Withdrawal: Pathogen-specific TLR2 protein activation programs macrophages to induce Wnt-{beta}-catenin signaling. [Withdrawals/Retractions]
This article has been withdrawn by the authors. After analysis of the original data used for assembling the figures in the article, the following issues were identified. Immunohistochemistry images demonstrating levels of COX-2 in TBM patients 1, 2, and 4 in Fig. 2E were duplicated as β-catenin in TBM patients 1, 4, and 3 in Fig. 2B. In Fig. 6D, immunohistochemistry images arising from the same experiment for iNOS−/−-BCG were used in Exp. 1 and 2. The authors state that the duplications occurred during primary assembly of the figures. The authors contacted the Journal, brought these errors to their attenti...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Kushagra Bansal, Jamma Trinath, Dipshikha Chakravortty, Shripad A. Patil, Kithiganahalli Narayanaswamy Balaji Tags: Withdrawals/Retractions Source Type: research

Withdrawal: Cooperative regulation of NOTCH1 protein-phosphatidylinositol 3-kinase (PI3K) signaling by NOD1, NOD2, and TLR2 receptors renders enhanced refractoriness to transforming growth factor-{beta} (TGF-{beta})- or cytotoxic T-lymphocyte antigen 4 (CTLA-4)-mediated impairment of human dendritic cell maturation. [Withdrawals/Retractions]
This article has been withdrawn by the authors. The authors identified some issues and brought them to the attention of the Journal. After careful analysis of all of the original data used for preparing the figures in the publication, the following errors were identified. The actin immunoblot from Fig. 6B was reused in Figs. 9C, 10C, and 11H. The actin immunoblot in Fig. 8B was reused in Fig. 11 (A and E). The actin immunoblot in Fig. 11B was reused in Fig. 11G. The authors submitted to the Journal all of the correct actin immunoblots for all of the figures listed above. Given these issues, the authors state that the respo...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Devram Sampat Ghorpade, Srini V. Kaveri, Jagadeesh Bayry, Kithiganahalli Narayanaswamy Balaji Tags: Withdrawals/Retractions Source Type: research

Withdrawal: Orphan nuclear receptor Nur77 induces zinc finger protein GIOT-1 gene expression, and GIOT-1 acts as a novel corepressor of orphan nuclear receptor SF-1 via recruitment of HDAC2. [Withdrawals/Retractions]
This article has been withdrawn by the authors. The actin panels for siHDAC2-I and siHDAC2-IV in Fig. 7E were duplicated. Additionally, in Fig. 7E, a portion of the HDAC2 gel from siHDAC2-II was duplicated in siHDAC2-III and siHDAC2-IV. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Kwang-Hoon Song, Yun-Yong Park, Hae Jin Kee, Cheol Yi Hong, Yong-Soo Lee, Seung-Won Ahn, Hye-Jin Kim, Keesook Lee, Hyun Kook, In-Kyu Lee, Heung-Sik Choi Tags: Withdrawals/Retractions Source Type: research

Correction: CD38 produces nicotinic acid adenine dinucleotide phosphate in the lysosome. [Additions and Corrections]
VOLUME 293 (2018) PAGES 8151–8160There was an error in the abbreviation for NAADP. The correct full name for NAADP is nicotinic acid adenine dinucleotide phosphate. The title should therefore read “CD38 produces nicotinic acid adenine dinucleotide phosphate in the lysosome.” (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Cheng Fang, Ting Li, Ying Li, Guan Jie Xu, Qi Wen Deng, Ya Jie Chen, Yun Nan Hou, Hon Cheung Lee, Yong Juan Zhao Tags: Additions and Corrections Source Type: research

Correction: Ac2PIM-responsive miR-150 and miR-143 target receptor-interacting protein kinase 2 and transforming growth factor beta-activated kinase 1 to suppress NOD2-induced immunomodulators. [Additions and Corrections]
VOLUME 290 (2015) PAGES 26576–26586The actin immunoblot in the right panel of Fig. 5D was inadvertently duplicated from Fig. 3D. This error has now been corrected and does not affect the results or conclusions of the work.jbc;294/50/19446/FU1F1FU1 (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Praveen Prakhar, Sahana Holla, Devram Sampat Ghorpade, Martine Gilleron, Germain Puzo, Vibha Udupa, Kithiganahalli Narayanaswamy Balaji Tags: Additions and Corrections Source Type: research

Correction: The multifunctional PE_PGRS11 protein from Mycobacterium tuberculosis plays a role in regulating resistance to oxidative stress. [Additions and Corrections]
VOLUME 285 (2010) PAGES 30389–30403The PE_PGRS11 immunoblots in Fig. 5 (A(i) and B) contained undeclared gel splices. The SDS-polyacrylamide gel in Fig. S2A also contained undeclared gel splices. These errors have now been corrected and do not affect the results or conclusions of the work.jbc;294/50/19445/F5F1F5Figure 5jbc;294/50/19445/FS2F2FS2Figure S2 (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Rashmi Chaturvedi, Kushagra Bansal, Yeddula Narayana, Nisha Kapoor, Namineni Sukumar, Shambhuprasad Kotresh Togarsimalemath, Nagasuma Chandra, Saurabh Mishra, Parthasarathi Ajitkumar, Beenu Joshi, Vishwa Mohan Kotach, Shripad A. Patil, Kithiganahalli Nara Tags: Additions and Corrections Source Type: research

Correction: NOTCH1 up-regulation and signaling involved in Mycobacterium bovis BCG-induced SOCS3 expression in macrophages. [Additions and Corrections]
VOLUME 283 (2008) PAGES 12501–12511There were several errors in this article. In Fig. 1G, the SOCS3 and actin immunoblots contained an undeclared gel splice. This error has now been corrected with replicate data. The data shown in Fig. 1 (H and I) are derived from the same experiment. The left lane of Fig. 1H should have also indicated BCG treatment. Figs. 1J and 2D contained undeclared gel splices. The p4EBP1 immunoblot in Fig. 2F and the SOCS3 immunoblot in Fig. 3H contained undeclared gel splices. Additionally, the 4EBP1 immunoblot in Fig. 2F and the actin immunoblot in Fig. 3H showed the incorrect lanes. These er...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Yeddula Narayana, Kithiganahalli Narayanaswamy Balaji Tags: Additions and Corrections Source Type: research

Designing protein structures and complexes with the molecular modeling program Rosetta [Computational Biology]
Proteins perform an amazingly diverse set of functions in all aspects of life. Critical to the function of many proteins are the highly specific three-dimensional structures they adopt. For this reason, there is strong interest in learning how to rationally design proteins that adopt user-defined structures. Over the last 25 years, there has been significant progress in the field of computational protein design as rotamer-based sequence optimization protocols have enabled accurate design of protein tertiary and quaternary structure. In this award article, I will summarize how the molecular modeling program Rosetta is used ...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Brian Kuhlman Tags: ASBMB Award Articles Source Type: research

The neural stem cell/carnitine malnutrition hypothesis: new prospects for effective reduction of autism risk? [Developmental Biology]
Autism spectrum disorders (ASDs) are developmental neuropsychiatric disorders with heterogeneous etiologies. As the incidence of these disorders is rising, such disorders represent a major human health problem with escalating social cost. Although recent years witnessed advances in our understanding of the genetic basis of some dysmorphic ASDs, little progress has been made in translating the improved understanding into effective strategies for ASD management or minimization of general ASD risk. Here we explore the idea, described in terms of the neural stem cell (NSC)/carnitine malnutrition hypothesis, that an unappreciat...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Vytas A. Bankaitis, Zhigang Xie Tags: ASBMB Award Articles Source Type: research

Substrate structure-activity relationship reveals a limited lipopolysaccharide chemotype range for intestinal alkaline phosphatase [Enzymology]
Lipopolysaccharide (LPS) from the Gram-negative bacterial outer membrane potently activates the human innate immune system. LPS is recognized by the Toll-like receptor 4/myeloid differentiation factor-2 (TLR4/MD2) complex, leading to the release of pro-inflammatory cytokines. Alkaline phosphatase (AP) is currently being investigated as an anti-inflammatory agent for detoxifying LPS through dephosphorylating lipid A, thus providing a potential treatment for managing both acute (sepsis) and chronic (metabolic endotoxemia) pathologies wherein aberrant TLR4/MD2 activation has been implicated. Endogenous LPS preparations are ch...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Gloria Komazin, Michael Maybin, Ronald W. Woodard, Thomas Scior, Dominik Schwudke, Ursula Schombel, Nicolas Gisch, Uwe Mamat, Timothy C. Meredith Tags: Microbiology Source Type: research

Pannexin 1 mediates ferroptosis that contributes to renal ischemia/reperfusion injury [Molecular Bases of Disease]
Renal ischemia/reperfusion injury (IRI) is a significant challenge in perioperative medicine and is related to oxidative programmed cell death. However, the role of ferroptosis, a newly discovered form of oxidative cell death, has not been evaluated widely. Pannexin 1 (PANX1), an ATP-releasing pathway family protein, has pro-apoptotic effects during kidney injury. Here, we demonstrate that PANX1 deletion protects against renal IRI by regulating ferroptotic cell death. Panx1 knockout mice subjected to renal IRI had decreased plasma creatinine, malondialdehyde (MDA) levels in kidney tissues, and tubular cell death (visible a...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Lianjiu Su, Xiaofang Jiang, Cheng Yang, Jiahao Zhang, Bo Chen, Yiming Li, Shijie Yao, Qin Xie, Hernando Gomez, Raghavan Murugan, Zhiyong Peng Tags: Cell Biology Source Type: research

Independent tubulin binding and polymerization by the proline-rich region of Tau is regulated by Tau's N-terminal domain [Protein Structure and Folding]
Tau is an intrinsically disordered, microtubule-associated protein that has a role in regulating microtubule dynamics. Despite intensive research, the molecular mechanisms of Tau-mediated microtubule polymerization are poorly understood. Here we used single-molecule fluorescence to investigate the role of Tau's N-terminal domain (NTD) and proline-rich region (PRR) in regulating interactions of Tau with soluble tubulin. We assayed both full-length Tau isoforms and truncated variants for their ability to bind soluble tubulin and stimulate microtubule polymerization. We found that Tau's PRR is an independent tubulin-binding d...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Kristen M. McKibben, Elizabeth Rhoades Tags: Molecular Biophysics Source Type: research

The ribosome assembly factor Nop53 controls association of the RNA exosome with pre-60S particles in yeast [RNA]
Eukaryotic ribosomal biogenesis is a high-energy–demanding and complex process that requires hundreds of trans-acting factors to dynamically build the highly-organized 40S and 60S subunits. Each ribonucleoprotein complex comprises specific rRNAs and ribosomal proteins that are organized into functional domains. The RNA exosome complex plays a crucial role as one of the pre-60S–processing factors, because it is the RNase responsible for processing the 7S pre-rRNA to the mature 5.8S rRNA. The yeast pre-60S assembly factor Nop53 has previously been shown to associate with the nucleoplasmic pre-60S in a region cont...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Leidy Paola P. Cepeda, Felipe F. M. Bagatelli, Renata M. Santos, Marlon D. M. Santos, Fabio C. S. Nogueira, Carla C. Oliveira Tags: Gene Regulation Source Type: research

Engineering chitinolytic activity into a cellulose-active lytic polysaccharide monooxygenase provides insights into substrate specificity [Enzymology]
Lytic polysaccharide monooxygenases (LPMOs) catalyze oxidative cleavage of recalcitrant polysaccharides such as cellulose and chitin and play an important role in the enzymatic degradation of biomass. Although it is clear that these monocopper enzymes have extended substrate-binding surfaces for interacting with their fibrous substrates, the structural determinants of LPMO substrate specificity remain largely unknown. To gain additional insight into substrate specificity in LPMOs, here we generated a mutant library of a cellulose-active family AA10 LPMO from Streptomyces coelicolor A3(2) (ScLPMO10C, also known as CelS2) ha...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Marianne Slang Jensen, Geir Klinkenberg, Bastien Bissaro, Piotr Chylenski, Gustav Vaaȷe–Kolstad, Hans Fredrik Kvitvang, Guro Kruge Nardal, Havard Sletta, Zarah Forsberg, Vincent G. H. Eiȷsink Tags: Enzymology Source Type: research

SDF2-like protein 1 (SDF2L1) regulates the endoplasmic reticulum localization and chaperone activity of ERdj3 protein [Cell Biology]
Molecular chaperones facilitate protein folding by associating with nascent polypeptides, thereby preventing protein misfolding and aggregation. Endoplasmic reticulum (ER) chaperone BiP, the sole HSP70 chaperone in the ER, is regulated by HSP40 chaperones, including ER-resident protein ERdj3 (DNAJB11). ERdj3 lacks an ER retrieval signal, is secreted under ER stress conditions, and functions as a chaperone in the extracellular space, but how its secretion is regulated remains unclear. We recently showed that ERdj3 forms a complex with ER-resident stromal cell–derived factor 2 (SDF2) and SDF2L1 (SDF2-like protein 1) an...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Ken Hanafusa, Ikuo Wada, Nobuko Hosokawa Tags: Protein Synthesis and Degradation Source Type: research

An engineered antibody fragment targeting mutant {beta}-catenin via maȷor histocompatibility complex I neoantigen presentation [Immunology]
Mutations in CTNNB1, the gene encoding β-catenin, are common in colon and liver cancers, the most frequent mutation affecting Ser-45 in β-catenin. Peptides derived from WT β-catenin have previously been shown to be presented on the cell surface as part of major histocompatibility complex (MHC) class I, suggesting an opportunity for targeting this common driver gene mutation with antibody-based therapies. Here, crystal structures of both the WT and S45F mutant peptide bound to HLA-A*03:01 at 2.20 and 2.45 Å resolutions, respectively, confirmed the accessibility of the phenylalanine residue for antibody ...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Michelle S. Miller, Jacqueline Douglass, Michael S. Hwang, Andrew D. Skora, Michael Murphy, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Shibin Zhou, Sandra B. Gabelli Tags: Molecular Biophysics Source Type: research

Enhanced acyl-CoA:cholesterol acyltransferase activity increases cholesterol levels on the lipid droplet surface and impairs adipocyte function [Metabolism]
Cholesterol plays essential structural and signaling roles in mammalian cells, but too much cholesterol can cause cytotoxicity. Acyl-CoA:cholesterol acyltransferases 1 and 2 (ACAT1/2) convert cholesterol into its storage form, cholesteryl esters, regulating a key step in cellular cholesterol homeostasis. Adipose tissue can store>50% of whole-body cholesterol. Interestingly, however, almost no ACAT activity is present in adipose tissue, and most adipose cholesterol is stored in its free form. We therefore hypothesized that increased cholesterol esterification may have detrimental effects on adipose tissue function. Here,...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Yanqing Xu, Ximing Du, Nigel Turner, Andrew J. Brown, Hongyuan Yang Tags: Lipids Source Type: research

Contribution of a mitochondrial tyrosyl-tRNA synthetase mutation to the phenotypic expression of the deafness-associated tRNASer(UCN) 7511A>G mutation [Molecular Bases of Disease]
Nuclear modifier genes have been proposed to modify the phenotypic expression of mitochondrial DNA mutations. Using a targeted exome-sequencing approach, here we found that the p.191Gly>Val mutation in mitochondrial tyrosyl-tRNA synthetase 2 (YARS2) interacts with the tRNASer(UCN) 7511A>G mutation in causing deafness. Strikingly, members of a Chinese family bearing both the YARS2 p.191Gly>Val and m.7511A>G mutations displayed much higher penetrance of deafness than those pedigrees carrying only the m.7511A>G mutation. The m.7511A>G mutation changed the A4:U69 base-pairing to G4:U69 pairing at the aminoacy...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Wenlu Fan, Jing Zheng, Wanzhong Kong, Limei Cui, Maerhaba Aishanjiang, Qiuzi Yi, Min Wang, Xiaohui Cang, Xiaowen Tang, Ye Chen, Jun Qin Mo, Neal Sondheimer, Wanzhong Ge, Min-Xin Guan Tags: RNA Source Type: research

Residues and residue pairs of evolutionary importance differentially direct signaling bias of D2 dopamine receptors [Protein Structure and Folding]
The D2 dopamine receptor and the serotonin 5-hydroxytryptamine 2A receptor (5-HT2A) are closely-related G-protein–coupled receptors (GPCRs) from the class A bioamine subfamily. Despite structural similarity, they respond to distinct ligands through distinct downstream pathways, whose dysregulation is linked to depression, bipolar disorder, addiction, and psychosis. They are important drug targets, and it is important to understand how their bias toward G-protein versus β-arrestin signaling pathways is regulated. Previously, evolution-based computational approaches, difference Evolutionary Trace and Evolutionary ...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Maria E. Terron–Diaz, Sara J. Wright, Melina A. Agosto, Olivier Lichtarge, Theodore G. Wensel Tags: Signal Transduction Source Type: research

Structural comparisons of phosphoenolpyruvate carboxykinases reveal the evolutionary trajectories of these phosphodiester energy conversion enzymes [Metabolism]
Inorganic pyrophosphate (PPi) consists of two phosphate molecules and can act as an energy and phosphate donor in cellular reactions, similar to ATP. Several kinases use PPi as a substrate, and these kinases have recently been suggested to have evolved from ATP-dependent functional homologs, which have significant amino acid sequence similarity to PPi-utilizing enzymes. In contrast, phosphoenolpyruvate carboxykinase (PEPCK) can be divided into three types according to the phosphate donor (ATP, GTP, or PPi), and the amino acid sequence similarity of these PEPCKs is too low to confirm that they share a common ancestor. Here ...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Yoko Chiba, Takuya Miyakawa, Yasuhiro Shimane, Ken Takai, Masaru Tanokura, Tomoyoshi Nozaki Tags: Enzymology Source Type: research

The RNA polymerase III repressor MAF1 is regulated by ubiquitin-dependent proteasome degradation and modulates cancer drug resistance and apoptosis [Gene Regulation]
MAF1 homolog, negative regulator of RNA polymerase III (MAF1) is a key repressor of RNA polymerase (pol) III–dependent transcription and functions as a tumor suppressor. Its expression is frequently down-regulated in primary human hepatocellular carcinomas (HCCs). However, this reduction in MAF1 protein levels does not correlate with its transcript levels, indicating that MAF1 is regulated post-transcriptionally. Here, we demonstrate that MAF1 is a labile protein whose levels are regulated through the ubiquitin-dependent proteasome pathway. We found that MAF1 ubiquitination is enhanced upon mTOR complex 1 (TORC1)&nda...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Xianlong Wang, Aleksandra Rusin, Christopher J. Walkey, Justin J. Lin, Deborah L. Johnson Tags: Cell Biology Source Type: research

GAIN domain-mediated cleavage is required for activation of G protein-coupled receptor 56 (GPR56) by its natural ligands and a small-molecule agonist [Cell Biology]
Adhesion G protein–coupled receptors (aGPCRs) represent a distinct family of GPCRs that regulate several developmental and physiological processes. Most aGPCRs undergo GPCR autoproteolysis-inducing domain–mediated protein cleavage, which produces a cryptic tethered agonist (termed Stachel (stinger)), and cleavage-dependent and -independent aGPCR signaling mechanisms have been described. aGPCR G1 (ADGRG1 or G protein–coupled receptor 56 (GPR56)) has pleiotropic functions in the development of multiple organ systems, which has broad implications for human diseases. To date, two natural GPR56 ligands, collag...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Beika Zhu, Rong Luo, Peng Jin, Tao Li, Hayeon C. Oak, Stefanie Giera, Kelly R. Monk, Parnian Lak, Brian K. Shoichet, Xianhua Piao Tags: Neurobiology Source Type: research

Changes in protein function underlie the disease spectrum in patients with CHIP mutations [Neurobiology]
In this study, we examined relationships between the clinical phenotypes of SCAR16 patients and the changes in biophysical, biochemical, and functional properties of the corresponding mutated protein. We found that the severity of ataxia did not correlate with age of onset; however, cognitive dysfunction, increased tendon reflex, and ancestry were able to predict 54% of the variation in ataxia severity. We further identified domain-specific relationships between biochemical changes in CHIP and clinical phenotypes and specific biochemical activities that associate selectively with either increased tendon reflex or cognitive...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Sabrina C. Madrigal, Zipporah McNeil, Rebekah Sanchez-Hodge, Chang-he Shi, Cam Patterson, Kenneth Matthew Scaglione, Jonathan C. Schisler Tags: Molecular Bases of Disease Source Type: research

The regulatory TnaC nascent peptide preferentially inhibits release factor 2-mediated hydrolysis of peptidyl-tRNA [Protein Synthesis and Degradation]
The tnaC regulatory gene from the tna operon of Escherichia coli controls the transcription of its own operon through an attenuation mechanism relying on the accumulation of arrested ribosomes during inhibition of its own translation termination. This free l-Trp–dependent mechanism of inhibition of translation termination remains unclear. Here, we analyzed the inhibitory effects of l-Trp on the function of two known E. coli translation termination factors, RF1 and RF2. Using a series of reporter genes, we found that the in vivo l-Trp sensitivity of tnaC gene expression is influenced by the identity of its stop codon,...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Jerusha Salome Emmanuel, Arnab Sengupta, Emily Roth Gordon, Joseph Thomas Noble, Luis Rogelio Cruz-Vera Tags: Gene Regulation Source Type: research

Trophectoderm regeneration to support full-term development in the inner cell mass isolated from bovine blastocyst [Developmental Biology]
Which comes first: tissue structure or cell differentiation? Although different cell types establish distinct structures delineating the inside and outside of an embryo, they progressively become specified by the blastocyst stage, when two types of cell lineages are formed: the inner cell mass (ICM) and the trophectoderm (TE). This inside–outside aspect can be experimentally converted by the isolation of the ICM from a blastocyst, leading to a posteriori externalization of the blastomeres composing the outermost layer of the ICM. Here, we investigated the totipotency of isolated mouse and bovine ICMs to determine whe...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Nanami Kohri, Hiroki Akizawa, Sakie Iisaka, Hanako Bai, Yojiro Yanagawa, Masashi Takahashi, Masaya Komatsu, Masahito Kawai, Masashi Nagano, Manabu Kawahara Tags: Developmental Biology Source Type: research

The solute carriers ZIP8 and ZIP14 regulate manganese accumulation in brain microvascular endothelial cells and control brain manganese levels [Neurobiology]
In this study, we have determined that ZIP8 and ZIP14 (Zrt- and Irt-like proteins 8 and 14) support Mn2+ uptake by BMVECs and that neither DMT1 nor an endocytosis-dependent pathway play any significant role in Mn2+ uptake. Specifically, siRNA-mediated knockdown of ZIP8 and ZIP14 coincided with a decrease in manganese uptake, and kinetic analyses revealed that manganese uptake depends on pH and bicarbonate and is up-regulated by lipopolysaccharide, all biochemical markers of ZIP8 or ZIP14 activity. Mn2+ uptake also was associated with cell-surface membrane presentation of ZIP8 and ZIP14, as indicated by membrane protein bio...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Brittany L. Steimle, Frances M. Smith, Daniel J. Kosman Tags: Cell Biology Source Type: research

The cytoplasmic domain of MxiG interacts with MxiK and directs assembly of the sorting platform in the Shigella type III secretion system [Protein Structure and Folding]
Many Gram-negative bacteria use type III secretion systems (T3SSs) to inject virulence effector proteins into eukaryotic cells. The T3SS apparatus (T3SA) is structurally conserved among diverse bacterial pathogens and consists of a cytoplasmic sorting platform, an envelope-spanning basal body, and an extracellular needle with tip complex. The sorting platform is essential for effector recognition and powering secretion. Studies using bacterial “minicells” have revealed an unprecedented level of structural detail of the sorting platform; however, many of the structure-function relationships within this complex r...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Shoichi Tachiyama, Yunjie Chang, Meenakumari Muthuramalingam, Bo Hu, Michael L. Barta, Wendy L. Picking, Jun Liu, William D. Picking Tags: Microbiology Source Type: research

Noncompetitive binding of PpiD and YidC to the SecYEG translocon expands the global view on the SecYEG interactome in Escherichia coli [Membrane Biology]
The SecYEG translocon constitutes the major protein transport channel in bacteria and transfers an enormous variety of different secretory and inner-membrane proteins. The minimal core of the SecYEG translocon consists of three inner-membrane proteins, SecY, SecE, and SecG, which, together with appropriate targeting factors, are sufficient for protein transport in vitro. However, in vivo the SecYEG translocon has been shown to associate with multiple partner proteins, likely allowing the SecYEG translocon to process its diverse substrates. To obtain a global view on SecYEG plasticity in Escherichia coli, here we performed ...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Benjamin Jauss, Narcis-Adrian Petriman, Friedel Drepper, Lisa Franz, Ilie Sachelaru, Thomas Welte, Ruth Steinberg, Bettina Warscheid, Hans-Georg Koch Tags: Membrane Biology Source Type: research

SUMOylation down-regulates rDNA transcription by repressing expression of upstream-binding factor and proto-oncogene c-Myc [DNA and Chromosomes]
Ribosome biogenesis is critical for proliferating cells and requires the coordinated activities of three eukaryotic RNA polymerases. We recently showed that the small ubiquitin-like modifier (SUMO) system controls the global level of RNA polymerase II (Pol II)–controlled transcription in mammalian cells by regulating cyclin-dependent kinase 9 activity. Here, we present evidence that the SUMO system also plays a critical role in the control of Pol I transcription. Using an siRNA-based knockdown approach, we found that multiple SUMO E3 ligases of the PIAS (protein inhibitor of activated STAT) family are involved in SUM...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Yu Peng, Zhenxing Wang, Zhiqiang Wang, Fang Yu, Jiwen Li, Jiemin Wong Tags: Gene Regulation Source Type: research

Photic generation of 11-cis-retinal in bovine retinal pigment epithelium [Enzymology]
Photoisomerization of the 11-cis-retinal chromophore of rod and cone visual pigments to an all-trans-configuration is the initiating event for vision in vertebrates. The regeneration of 11-cis-retinal, necessary for sustained visual function, is an endergonic process normally conducted by specialized enzyme systems. However, 11-cis-retinal also can be formed through reverse photoisomerization from all-trans-retinal. A nonvisual opsin known as retinal pigment epithelium (RPE)-retinal G-protein–coupled receptor (RGR) was previously shown to mediate visual chromophore regeneration in photic conditions, but conflicting r...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Jianye Zhang, Elliot H. Choi, Aleksander Tworak, David Salom, Henri Leinonen, Christopher L. Sander, Thanh V. Hoang, James T. Handa, Seth Blackshaw, Grazyna Palczewska, Philip D. Kiser, Krzysztof Palczewski Tags: Enzymology Source Type: research

The myosin-tail homology domain of centrosomal protein 290 is essential for protein confinement between the inner and outer segments in photoreceptors [Cell Biology]
Mutations in the centrosomal protein 290 (CEP290) gene cause various ciliopathies involving retinal degeneration. CEP290 proteins localize to the ciliary transition zone and are thought to act as a gatekeeper that controls ciliary protein trafficking. However, precise roles of CEP290 in photoreceptors and pathomechanisms of retinal degeneration in CEP290-associated ciliopathies are not sufficiently understood. Using conditional Cep290 mutant mice, in which the C-terminal myosin-tail homology domain of CEP290 is disrupted after the connecting cilium is assembled, we show that this domain is essential for protein confinement...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Poppy Datta, Brandon Hendrickson, Sarah Brendalen, Avri Ruffcorn, Seongjin Seo Tags: Molecular Bases of Disease Source Type: research

Facile autofluorescence suppression enabling tracking of single viruses in live cells [Methods and Resources]
Live cell fluorescence imaging is the method of choice for studying dynamic processes, such as nuclear transport, vesicular trafficking, and virus entry and egress. However, endogenous cellular autofluorescence masks a useful fluorescence signal, limiting the ability to reliably visualize low-abundance fluorescent proteins. Here, we employed synchronously amplified fluorescence image recovery (SAFIRe), which optically alters ground versus photophysical dark state populations within fluorescent proteins to modulate and selectively detect their background-free emission. Using a photoswitchable rsFastLime fluorescent protein ...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Yen-Cheng Chen, Chetan Sood, Ashwanth C. Francis, Gregory B. Melikyan, Robert M. Dickson Tags: Microbiology Source Type: research

Primary cilia and the exocyst are linked to urinary extracellular vesicle production and content [Cell Biology]
The recently proposed idea of “urocrine signaling” hypothesizes that small secreted extracellular vesicles (EVs) contain proteins that transmit signals to distant cells. However, the role of renal primary cilia in EV production and content is unclear. We previously showed that the exocyst, a highly conserved trafficking complex, is necessary for ciliogenesis; that it is present in human urinary EVs; that knockdown (KD) of exocyst complex component 5 (EXOC5), a central exocyst component, results in very short or absent cilia; and that human EXOC5 overexpression results in longer cilia. Here, we show that compare...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Xiaofeng Zuo, Sang-Ho Kwon, Michael G. Janech, Yujing Dang, Steven D. Lauzon, Ben Fogelgren, Noemi Polgar, Joshua H. Lipschutz Tags: Cell Biology Source Type: research

Functional diversification of the chemical landscapes of yeast Sec14-like phosphatidylinositol transfer protein lipid-binding cavities [Signal Transduction]
Phosphatidylinositol-transfer proteins (PITPs) are key regulators of lipid signaling in eukaryotic cells. These proteins both potentiate the activities of phosphatidylinositol (PtdIns) 4-OH kinases and help channel production of specific pools of phosphatidylinositol 4-phosphate (PtdIns(4)P) dedicated to specific biological outcomes. In this manner, PITPs represent a major contributor to the mechanisms by which the biological outcomes of phosphoinositide are diversified. The two-ligand priming model proposes that the engine by which Sec14-like PITPs potentiate PtdIns kinase activities is a heterotypic lipid-exchange cycle ...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Ashutosh Tripathi, Elliott Martinez, Ahmad J. Obaidullah, Marta G. Lete, Max Lonnfors, Danish Khan, Krishnakant G. Soni, Carl J. Mousley, Glen E. Kellogg, Vytas A. Bankaitis Tags: Lipids Source Type: research

Structure-function relationships underlying the dual N-acetylmuramic and N-acetylglucosamine specificities of the bacterial peptidoglycan deacetylase PdaC [Protein Structure and Folding]
Bacillus subtilis PdaC (BsPdaC) is a membrane-bound, multidomain peptidoglycan N-deacetylase acting on N-acetylmuramic acid (MurNAc) residues and conferring lysozyme resistance to modified cell wall peptidoglycans. BsPdaC contains a C-terminal family 4 carbohydrate esterase (CE4) catalytic domain, but unlike other MurNAc deacetylases, BsPdaC also has GlcNAc deacetylase activity on chitooligosaccharides (COSs), characteristic of chitin deacetylases. To uncover the molecular basis of this dual activity, here we determined the X-ray structure of the BsPdaC CE4 domain at 1.54 Å resolution and analyzed its mode of action ...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Laia Grifoll–Romero, Maria Angela Sainz–Polo, David Albesa–Jove, Marcelo E. Guerin, Xevi Biarnes, Antoni Planas Tags: Enzymology Source Type: research

Humanin induces conformational changes in the apoptosis regulator BAX and sequesters it into fibers, preventing mitochondrial outer-membrane permeabilization [Protein Structure and Folding]
The mitochondrial, or intrinsic, apoptosis pathway is regulated mainly by members of the B-cell lymphoma 2 (BCL-2) protein family. BCL-2–associated X apoptosis regulator (BAX) plays a pivotal role in the initiation of mitochondria-mediated apoptosis as one of the factors causing mitochondrial outer-membrane permeabilization (MOMP). Of current interest are endogenous BAX ligands that inhibit its MOMP activity. Mitochondrial-derived peptides (MDPs) are a recently identified class of mitochondrial retrograde signaling molecules and are reported to be potent apoptosis inhibitors. Among them, humanin (HN) has been shown t...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Daniel L. Morris, David W. Kastner, Sabrina Johnson, Marie-Paule Strub, Yi He, Christopher K. E. Bleck, Duck-Yeon Lee, Nico Tjandra Tags: Molecular Biophysics Source Type: research

Translesion synthesis DNA polymerases {eta}, {iota}, and {nu} promote mutagenic replication through the anticancer nucleoside cytarabine [DNA and Chromosomes]
Cytarabine (AraC) is the mainstay for the treatment of acute myeloid leukemia. Although complete remission is observed in a large proportion of patients, relapse occurs in almost all the cases. The chemotherapeutic action of AraC derives from its ability to inhibit DNA synthesis by the replicative polymerases (Pols); the replicative Pols can insert AraCTP at the 3′ terminus of the nascent DNA strand, but they are blocked at extending synthesis from AraC. By extending synthesis from the 3′-terminal AraC and by replicating through AraC that becomes incorporated into DNA, translesion synthesis (TLS) DNA Pols could...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Jung-Hoon Yoon, Jayati Roy Choudhury, Louise Prakash, Satya Prakash Tags: DNA and Chromosomes Source Type: research

Multiple mitochondrial thioesterases have distinct tissue and substrate specificity and CoA regulation, suggesting unique functional roles [Lipids]
Acyl-CoA thioesterases (Acots) hydrolyze fatty acyl-CoA esters. Acots in the mitochondrial matrix are poised to mitigate β-oxidation overload and maintain CoA availability. Several Acots associate with mitochondria, but whether they all localize to the matrix, are redundant, or have different roles is unresolved. Here, we compared the suborganellar localization, activity, expression, and regulation among mitochondrial Acots (Acot2, -7, -9, and -13) in mitochondria from multiple mouse tissues and from a model of Acot2 depletion. Acot7, -9, and -13 localized to the matrix, joining Acot2 that was previously shown to loca...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M. Herrmann, Erin L. Seifert Tags: Metabolism Source Type: research

Modified sites and functional consequences of 4-oxo-2-nonenal adducts in HDL that are elevated in familial hypercholesterolemia [Lipids]
The lipid aldehyde 4-oxo-2-nonenal (ONE) is a highly reactive protein crosslinker derived from peroxidation of n-6 polyunsaturated fatty acids and generated together with 4-hydroxynonenal (HNE). Lipid peroxidation product-mediated crosslinking of proteins in high-density lipoprotein (HDL) causes HDL dysfunction and contributes to atherogenesis. Although HNE is relatively well-studied, the role of ONE in atherosclerosis and in modifying HDL is unknown. Here, we found that individuals with familial hypercholesterolemia (FH) had significantly higher ONE-ketoamide (lysine) adducts in HDL (54.6 ± 33.8 pmol/mg) than healt...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Linda S. May-Zhang, Valery Yermalitsky, John T. Melchior, Jamie Morris, Keri A. Tallman, Mark S. Borja, Tiffany Pleasent, Venkataraman Amarnath, Wenliang Song, Patricia G. Yancey, W. Sean Davidson, MacRae F. Linton, Sean S. Davies Tags: Molecular Bases of Disease Source Type: research

Interactions of the effector ExoU from Pseudomonas aeruginosa with short-chain phosphatidylinositides provide insights into ExoU targeting to host membranes [Molecular Biophysics]
In this study, we used site-directed spin-labeling electron paramagnetic resonance spectroscopy to examine the interaction of ExoU with soluble analogs of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2). We found that dioctanoyl PI(4,5)P2 binds to and induces conformational changes in a C-terminal four-helix bundle (4HB) domain of ExoU implicated previously in membrane binding. Other soluble phosphoinositides also interacted with the 4HB but less effectively. Molecular modeling and ligand docking studies indicated the potential for numerous hydrogen bond interactions within and between interhelical loops of the 4HB and...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Tzvia I. Springer, Terry-Elinor Reid, Samantha L. Gies, Jimmy B. Feix Tags: Membrane Biology Source Type: research

Proper secretion of the serpin antithrombin relies strictly on thiol-dependent quality control [Protein Structure and Folding]
The protein quality control machinery of the endoplasmic reticulum (ERQC) ensures that client proteins are properly folded. ERQC substrates may be recognized as nonnative by the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans. How these features dictate which ERQC pathways engage a given substrate is poorly understood. Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells. Although ATIII has N-glycans and a hydrophobic core, we found that its quality con...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Benjamin M. Adams, Haiping Ke, Lila M. Gierasch, Anne Gershenson, Daniel N. Hebert Tags: Cell Biology Source Type: research

Two uptake hydrogenases differentially interact with the aerobic respiratory chain during mycobacterial growth and persistence [Microbiology]
To persist when nutrient sources are limited, aerobic soil bacteria metabolize atmospheric hydrogen (H2). This process is the primary sink in the global H2 cycle and supports the productivity of microbes in oligotrophic environments. H2-metabolizing bacteria possess [NiFe] hydrogenases that oxidize H2 to subatmospheric concentrations. The soil saprophyte Mycobacterium smegmatis has two such [NiFe] hydrogenases, designated Huc and Hhy, that belong to different phylogenetic subgroups. Both Huc and Hhy are oxygen-tolerant, oxidize H2 to subatmospheric concentrations, and enhance bacterial survival during hypoxia and carbon li...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Paul R. F. Cordero, Rhys Grinter, Kiel Hards, Max J. Cryle, Coral G. Warr, Gregory M. Cook, Chris Greening Tags: Bioenergetics Source Type: research

Cytoplasmic dsRNA induces the expression of OCT3/4 and NANOG mRNAs in differentiated human cells [Microbiology]
Cytoplasmic dsRNA is recognized by RNA helicase RIG-I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), triggering induction of the innate immune response via the mitochondrial antiviral signaling protein (MAVS). In contrast, extracellular dsRNA is internalized into endosomes and recognized by Toll-like receptor 3 (TLR3), which triggers signaling via the Toll-like receptor adaptor molecule 1 (TICAM-1). Poly(I:C) is a synthetic dsRNA analog and increases the expression of octamer-binding protein 3/4 (OCT3/4), NANOG, and SRY-box (SOX) mRNAs during pluripotency induction. However, the mechanism underlying this...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Guanming Wang, Takahisa Kouwaki, Kazuki Mugikura, Masaaki Okamoto, Hiromi Takaki, Kenji Funami, Tsukasa Seya, Hiroyuki Oshiumi Tags: Immunology Source Type: research

Leaky endosomes push tau over the seed limit [Molecular Bases of Disease]
The inter- and intracellular propagation of aggregated proteins like tau is emerging as a central mechanism behind progression of various neurodegenerative diseases. The steps by which tau aggregates and propagates is currently unclear. Chen et al. now combine a cell-based model of tau aggregation with a CRISPR interference (CRISPRi) genetic screen to identify components of the endosomal sorting complex required for transport (ESCRT) machinery as mediators of intracellular propagation of tau aggregates. These findings reveal a role for endolysosomal integrity in blocking tau propagation. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: Chris Ugbode, Laura Fort-Aznar, Sean T. Sweeney Tags: Editors ' Picks Highlights Source Type: research

Compromised function of the ESCRT pathway promotes endolysosomal escape of tau seeds and propagation of tau aggregation [Membrane Biology]
Intercellular propagation of protein aggregation is emerging as a key mechanism in the progression of several neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia (FTD). However, we lack a systematic understanding of the cellular pathways controlling prion-like propagation of aggregation. To uncover such pathways, here we performed CRISPR interference (CRISPRi) screens in a human cell-based model of propagation of tau aggregation monitored by FRET. Our screens uncovered that knockdown of several components of the endosomal sorting complexes required for transport (ESCRT) machinery, includin...
Source: Journal of Biological Chemistry - December 13, 2019 Category: Chemistry Authors: John J. Chen, Diane L. Nathaniel, Preethi Raghavan, Maxine Nelson, Ruilin Tian, Eric Tse, Jason Y. Hong, Stephanie K. See, Sue-Ann Mok, Marco Y. Hein, Daniel R. Southworth, Lea T. Grinberg, Jason E. Gestwicki, Manuel D. Leonetti, Martin Kampmann Tags: Editors ' Picks Source Type: research

Correction: The host-cell restriction factor SERINC5 restricts HIV-1 infectivity without altering the lipid composition and organization of viral particles. [Additions and Corrections]
VOLUME 292 (2017) PAGES 13702–13713A funding source was inadvertently omitted. The following should be added to the grant footnote. H. W. and B. B. were supported by the German Research Foundation (DFG, Project Number 278001972–TRR 186). (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - December 6, 2019 Category: Chemistry Authors: Birthe Trautz, Hanna Wiedemann, Christian Luchtenborg, Virginia Pierini, Jan Kranich, Barbel Glass, Hans–Georg Krausslich, Thomas Brocker, Massimo Pizzato, Alessia Ruggieri, Britta Brugger, Oliver T. Fackler Tags: Additions and Corrections Source Type: research

Withdrawal: DDR1 receptor tyrosine kinase promotes prosurvival pathway through Notch1 activation. [Withdrawals/Retractions]
This article has been withdrawn by the authors. An investigation by Harvard Medical School and Massachusetts General Hospital determined that the DDR1 and actin immunoblots in Fig. 2B (right panels) were reused in Fig. 6A. In addition, the Journal raised questions regarding the merged image for control cells in Fig. 4D. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - December 6, 2019 Category: Chemistry Authors: Hyung-Gu Kim, So-Young Hwang, Stuart A. Aaronson, Anna Mandinova, Sam W. Lee Tags: Withdrawals/Retractions Source Type: research

Withdrawal: Nuclear localization and in situ DNA damage by Mycobacterium tuberculosis nucleoside-diphosphate kinase. [Withdrawals/Retractions]
This article has been withdrawn by the authors. Lanes 2–4 of Fig. 4A were reused in Fig. 5C. Lanes 1 and 2 of Fig. 4B were reused as lanes 2 and 3 of Fig. 7B. Lanes 5 and 6 of Fig. 4C were reused in Fig. 5D. Lanes 1 and 2 of Fig. 5A were reused in Fig. 5B. The authors state that several gels were run for each experiment and that the images were cropped to create panels. They further state that the wrong panels were selected while assembling the figures as they appeared very similar. The authors assert that these errors do not change the results of this article. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - December 6, 2019 Category: Chemistry Authors: Adesh Kumar Saini, Kapil Maithal, Prem Chand, Shantanu Chowdhury, Reena Vohra, Anita Goyal, Gyanendra P. Dubey, Puneet Chopra, Ramesh Chandra, Anil K. Tyagi, Yogendra Singh, Vibha Tandon Tags: Withdrawals/Retractions Source Type: research

On the mechanism of GIRK2 channel gating by phosphatidylinositol bisphosphate, sodium, and the G{beta}{gamma} dimer [Molecular Biophysics]
G protein–gated inwardly rectifying K+ (GIRK) channels belong to the inward-rectifier K+ (Kir) family, are abundantly expressed in the heart and the brain, and require that phosphatidylinositol bisphosphate is present so that intracellular channel-gating regulators such as Gβγ and Na+ ions can maintain the channel-open state. However, despite high-resolution structures (GIRK2) and a large number of functional studies, we do not have a coherent picture of how Gβγ and Na+ ions control gating of GIRK2 channels. Here, we utilized computational modeling and all-atom microsecond-scale molecular dynami...
Source: Journal of Biological Chemistry - December 6, 2019 Category: Chemistry Authors: Dailin Li, Taihao Jin, Dimitris Gazgalis, Meng Cui, Diomedes E. Logothetis Tags: Computational Biology Source Type: research

Characterization of NCS1-InsP3R1 interaction and its functional significance [Cell Biology]
In conclusion, we show that NCS1–InsP3R1 interaction enhances intracellular Ca2+ signaling in cells and can be modulated by altering or occluding the hydrophobic pocket of NCS1. This improved understanding of the NCS1–InsP3R1 interaction may facilitate the development of management strategies for diseases resulting from aberrant NCS1 expression. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - December 6, 2019 Category: Chemistry Authors: Lien D. Nguyen, Edward T. Petri, Larry K. Huynh, Barbara E. Ehrlich Tags: Signal Transduction Source Type: research