Reactivity of γ‐glutamyl‐cysteine with intracellular and extracellular glutathione metabolic enzymes
This study investigates whether gamma-glutamyl-cysteine ( γ-EC) functions as a substrate for glutathione (GSH) metabolic enzymes, which mediate the antioxidant defence. Glutathione peroxidase (GPx), glutathioneS-transferase (GST) and γ-glutamyl transferase (GGT) exhibited substrate specificity for γ-EC, whereas glutathione reductase (GR) did not. The specificities of γ-EC and its disulphide form to GGT were comparable to GSH and its oxidized form, GSSG respectively. Gamma-glutamyl-cysteine ( γ-EC) is a precursor of glutathione (GSH) biosynthesis. We investigated whether it functions as a subst...
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Authors: Misa Muraoka, Saki Yoshida, Moeka Ohno, Hideyuki Matsuura, Kazuya Nagano, Yoshihiko Hirata, Masayoshi Arai, Kazumasa Hirata Tags: Research Article Source Type: research

Front Cover
Cover illustration The cover image refers to the article “Sterol uptake by the NPC system in eukaryotes: a Saccharomyces cerevisiae perspective” by Winkleret al. (pp. 160 –179). (Source: FEBS Letters)
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Tags: Issue Information Source Type: research

Sterol uptake by the NPC system in eukaryotes: a Saccharomyces  cerevisiae perspective
Sterols are an essential component of eukaryotic membranes. After endocytotic uptake, sterols are integrated into membranes by the Niemann-Pick type C (NPC) system. The NPC system consists of two proteins: NPC2, a lysosomal sterol shuttle protein, and NPC1 (NCR1 in fungi), which integrates sterols into the lysosomal membrane. We propose a unifying conceptual model for sterol loading, transfer and transport by the NPC system. Sterols are an essential component of membranes in all eukaryotic cells and the precursor of multiple indispensable cellular metabolites. After endocytotic uptake, sterols are integrated into the lysos...
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Authors: Mikael B. L. Winkler, Lynette Nel, Kelly M. Frain, Emil Dedic, Esben Olesen, Bj ørn Panyella Pedersen Tags: Perspective Source Type: research

Corrigendum
(Source: FEBS Letters)
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Tags: Corrigendum Source Type: research

Front Cover
Cover illustration The cover image refers to the article “Sterol uptake by the NPC system in eukaryotes: a Saccharomyces cerevisiae perspective” by Winkleret al. (pp. 160 –179). (Source: FEBS Letters)
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Tags: Issue Information Source Type: research

Why science education is more important than most scientists think
The COVID-19 pandemic has revealed that a shockingly large fraction of the public is willing to ignore scientific judgements on issues such a vaccines and mask wearing. For far too many, scientific findings are viewed as what scientists believe, rather than as the product of an elaborate community process that produces reliable knowledge. This widespread misunderstanding should serve as a wake-up call for scientists, clearly demonstrating that the standard way that we teach science – as a large collection of “facts” that scientists have discovered about the world – needs major change. Three more amb...
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Authors: Bruce Alberts Tags: The Scientists' Forum Source Type: research

Structural basis for the recognition of the S2, S5 ‐phosphorylated RNA polymerase II CTD by the mRNA anti‐terminator protein hSCAF4
The S2, S5-phosphorylated RNA polymerase II C-terminal domain (CTD) can be recognized by the transcription factor SCAF4, which functions as an mRNA anti-terminator by preventing early mRNA transcript cleavage and polyadenylation. Here, we demonstrated that the hSCAF4-CTD-interaction domain (CID) prefers binding to the S2, S5-phosphorylated CTD, and we determined the structure of hSCAF4-CID in complex with an S2, S5-quadra-phosphorylated CTD peptide, providing insight into the regulatory mechanism of hSCAF4 in transcription termination. The C-terminal domain (CTD) of RNA polymerase II serves as a binding platform for numero...
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Authors: Mengqi Zhou, Fahad Ehsan, Linyao Gan, Aiping Dong, Yanjun Li, Ke Liu, Jinrong Min Tags: Research Article Source Type: research

Calcium regulates the interplay between the tight junction and epithelial adherens junction at the plasma membrane
Assembly of the apical junctional complex (AJC) is coordinated by calcium concentrations and the interplay between the adherens junction (AJ) and tight junction (TJ) membrane proteins. We show using a simple AJC, composed of epithelial cadherin in the AJ and claudin 1, occludin, and junctional adhesion molecule A in the TJ that these proteins have different interaction affinities that are calcium sensitive. The apical junctional complex (AJC) is a membrane protein ultrastructure that regulates cell adhesion and homeostasis. The tight junction (TJ) and the adherens junction (AJ) are substructures of the AJC. The interplay b...
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Authors: Christopher Mendoza, Sai Harsha Nagidi, Kjetil Collett, Jacob Mckell, Dario Mizrachi Tags: Research Letter Source Type: research

Recruitment of TNF ligands to lipid rafts is mediated by their physical association with caveolin ‐1
This study reveals that the TNF –caveolin-1 association may be responsible for recruiting TNF to lipid rafts. Activities of the tumour necrosis factor (TNF) family members are associated with their targeting to lipid rafts, specialised regions of the plasma membrane. Herein, we investigated the physical association of TNF and its family members cluster of differentiation 40 ligand (CD40L) and tumour necrosis factor-related apoptosis-inducing ligand with caveolin-1, a lipid raft resident protein. We discovered that the intracellular domains of TNF and CD40L interact with caveolin-1, and the membrane proximal region of...
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Authors: Xenia A. Glukhova, Julia A. Trizna, Bogdan S. Melnik, Olga V. Proussakova, Igor P. Beletsky Tags: Research Letter Source Type: research

Charged sequence motifs increase the propensity towards liquid ‐liquid phase separation
Protein phase separation is a major governing factor in multiple cellular processes, such as RNA metabolism and those involving RNA-binding proteins. In this work, we show that proteins harbouring sequence regions with specific charged residue patterns are significantly associated with liquid-liquid phase separation. In particular, regions with repetitive arrays of alternating charges show the strongest association. AbstractProtein phase separation is a major governing factor in multiple cellular processes, such as RNA metabolism and those involving RNA-binding proteins. Despite many key observations, the exact structural ...
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Authors: Andr ás László Szabó, Anna Sánta, Rita Pancsa, Zoltán Gáspári Tags: Research Article Source Type: research

A γ‐glutamyl hydrolase lacking the signal peptide confers susceptibility to folates/antifolates in acute lymphoblastic leukemia cells
In this study, we show that intact GGH is not indispensable for the chemosensitivity and growth of acute lymphoblastic leukemia (ALL) cells, whereas GGH lacking N-terminal signal peptide (GGH−ΔN) confers the significant drug resistance of ALL cells to the antifolates MTX and RTX. In addition, ALL cells harboring GGH−ΔN show high susceptibility to the change in folates, and glycosylation is not responsible for these phenotypes elicited by GGH−ΔN. Mechanistically, the loss of signal peptide enhances intracellular retention of GGH and its lysosomal disposition. Our findings clearly define t...
Source: FEBS Letters - January 24, 2022 Category: Biochemistry Authors: Shuxuan Wang, Yao Chen, Houshun Fang, Yan Xu, Ming Ding, Chunshuang Ma, Yanyan Lin, Zhiyan Cui, Huiying Sun, Qun Niu, Shuzhang Sun, Bin ‐Bing S. Zhou, Ning Xiao, Hui Li Tags: Research Article Source Type: research

The [2Fe ‐2S] protein CISD2 plays a key role in preventing iron accumulation in cardiomyocytes
The iron –sulfur cluster protein CISD2 plays a key role in regulating calcium homeostasis, preventing mitochondrial dysfunction, and heart failure (HF). Here, usingCISD2-null mice, we show that CISD2 is also protecting cardiomyocytes from overaccumulation of iron, which is common in aging hearts and can also contribute to the pathogenesis of HF. Considered a key aging gene,CISD2, encoding CDGSH iron –sulfur domain-containing protein 2, plays a central role in regulating calcium homeostasis, preventing mitochondrial dysfunction, and the activation of autophagy and apoptosis in different cells. Here, we show that...
Source: FEBS Letters - January 21, 2022 Category: Biochemistry Authors: Ola Karmi, Linda Rowland, Skylar D. King, Camila Manrique ‐Acevedo, Ioav Z. Cabantchik, Rachel Nechushtai, Ron Mittler Tags: Research Article Source Type: research

Novel and conventional inhibitors of canonical autophagy differently affect LC3 ‐associated phagocytosis
In this study, we dissected the effects of autophagy inhibitors on LAP. SAR405, an inhibitor of VPS34, reduced levels of LC3-II and inhibited LAP. In contrast, the inhibitors of endosomal acidification bafilomycin A1 and chloroquine increased levels of LC3-II, due to reduced degradation in acidic lysosomes. However, while bafilomycin A1 inhibited LAP, chloroquine did not. Finally, EACC, which inhibits the fusion of autophagosomes with lysosomes, promoted LC3 degradation possibly by the proteasome. Targeting LAP with small molecule inhibitors is important given its emerging role in infectious and autoimmune diseases. (Source: FEBS Letters)
Source: FEBS Letters - January 21, 2022 Category: Biochemistry Authors: Femmy C. Stempels, Maaike H. Janssens, Martin Beest, Rob J. Mesman, Natalia H. Revelo, Melina Ioannidis, Geert den Bogaart Tags: Research Article Source Type: research

Analyses of the complex formation of staphylococcal enterotoxin A and the human gp130 cytokine receptor
Here, the structural details of the complex between a bacterial superantigen (SEA) and human cytokine signaling receptor gp130 was analyzed. The data suggest that SEA may interact with human gp130 in a different manner than other gp130-ligands. Moreover, as SEA was shown to not bind rodent gp130, the interaction with human gp130 is speculated to be coupled to food poisoning. ABSTRACTSuperantigens (SAgs) are bacterial enterotoxins produced byStaphylococcus aureus. Staphylococcal enterotoxin type A (SEA), a staphylococcal superantigen, has been shown to bind to the cytokine signaling receptor glycoprotein 130 (gp130). The st...
Source: FEBS Letters - January 21, 2022 Category: Biochemistry Authors: Sibel Uzun ҫayır, Arturo Vera‐Rodriguez, Paulina Regenthal, Hannah Åbacka, Cecilia Emanuelsson, Christopher D. Bahl, Karin Lindkvist‐Petersson Tags: Research Article Source Type: research

A purine and a backbone discontinuous site alter the structure and thermal stability of DNA minidumbbells containing two pentaloops
This study presents the solution NMR structures of a DNA minidumbbell consisting of two regular CTTTG pentaloops. In the 3 ′-loop, substitution of the fourth thymine with an adenine residue or creation of a backbone discontinuous site between the third and fourth thymine residues enhanced the thermal stability of the minidumbbell structure. AbstractMinidumbbell (MDB) is a non-canonical DNA structure found to form in several pyrimidine-rich short tandem repeats associated with neurodegenerative diseases. The most recently reported MDB contains two pentaloops formed by ATTCT repeats. Here, we studied the effects of a p...
Source: FEBS Letters - January 21, 2022 Category: Biochemistry Authors: Cheuk Kit Ngai, Sik Lok Lam, Hung Kay Lee, Pei Guo Tags: Research Article Source Type: research

The role of exosomes in intercellular and inter ‐organ communication of the peripheral nervous system
Exosomes are extracellular vesicles that are produced via the endosomal pathway. They transport bioactive proteins, mRNAs and microRNA (miRNAs) in an active form to adjacent cells or to distant organs. In the peripheral nervous system, they are important mediators of inter-cellular communication during peripheral nerve homeostasis and regeneration as well as of the interaction with different other organ systems. Exosomes, nano-sized extracellular vesicles, are produced via the endosomal pathway and released in the extracellular space upon fusion of multivesicular bodies with the plasma membrane. Recent evidence shows that ...
Source: FEBS Letters - January 21, 2022 Category: Biochemistry Authors: Julia Patricia Bischoff, Alexander Schulz, Helen Morrison Tags: Review Source Type: research

IL ‐17RD/sef exacerbates experimental mouse colitis and inflammation‐associated tumorigenesis by regulating the proportion of T cell subsets
Using IL-17RD/Sef knockout mice, we identified that loss of IL-17RD/Sef alleviates experimental colonic inflammatory and colitis-induced colorectal tumorigenesis. IL-17RD/Sef exhibits the ability to activate Th1/17 cells whereas to inhibit Treg cells under inflammatory conditions, indicating that IL-17RD/Sef is a modulator for the immune cells balance. T helper cells, especially Th1 and Th17 cells, were reported to play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). However, the underlying factors regulating T cell functions in IBD progression remain to be fully elucidated. Here, we revealed that I...
Source: FEBS Letters - January 21, 2022 Category: Biochemistry Authors: Yanxia Fu, Sihan Liu, Mengdi Li, Fangli Ren, Yinyin Wang, Zhijie Chang Tags: Research Letter Source Type: research

Osteocalcin and the physiology of danger
The known functions of osteocalcin and the involvement of its three known receptors. The illustration shows that the physiological processes regulated by osteocalcin are needed to sense and escape danger, among other functions. Bone biology has long been driven by the question as to what molecules affect cell differentiation or the functions of bone. Exploring this issue has been an extraordinarily powerful way to improve our knowledge of bone development and physiology. More recently, a second question has emerged: does bone have other functions besides making bone? Addressing this conundrum revealed that the bone-derived...
Source: FEBS Letters - January 21, 2022 Category: Biochemistry Authors: Julian Meyer Berger, Gerard Karsenty Tags: Review Source Type: research

Analyses of the complex formation of staphylococcal enterotoxin A and the human gp130 cytokine receptor
Here, the structural details of the complex between a bacterial superantigen (SEA) and human cytokine signaling receptor gp130 was analyzed. The data suggest that SEA may interact with human gp130 in a different manner than other gp130-ligands. Moreover, as SEA was shown to not bind rodent gp130, the interaction with human gp130 is speculated to be coupled to food poisoning. ABSTRACTSuperantigens (SAgs) are bacterial enterotoxins produced byStaphylococcus aureus. Staphylococcal enterotoxin type A (SEA), a staphylococcal superantigen, has been shown to bind to the cytokine signaling receptor glycoprotein 130 (gp130). The st...
Source: FEBS Letters - January 21, 2022 Category: Biochemistry Authors: Sibel Uzun ҫayır, Arturo Vera‐Rodriguez, Paulina Regenthal, Hannah Åbacka, Cecilia Emanuelsson, Christopher D. Bahl, Karin Lindkvist‐Petersson Tags: Research Article Source Type: research

Interorgan crosstalk in pancreatic islet function and pathology
In this review, we discussed inter-organ signalling that is beneficial or detrimental to pancreatic islet function and survival. Distal metabolic organs, such as liver, adipose, intestine, bone and skeletal muscle, modulate islet function through a variety of circulating factors. Multiple components in the pancreatic microenvironment, including sympathetic/parasympathetic nerves, infiltrating immune cells and the exocrine compartment, also crosstalk with islet in both physiological and pathological settings. Pancreatic β cells secrete insulin in response to glucose, a process that is regulated at multiple levels, incl...
Source: FEBS Letters - January 20, 2022 Category: Biochemistry Authors: Ronald M. Evans, Zong Wei Tags: Review Source Type: research

Matching chemical properties to molecular biological activities opens a new perspective on l ‐ergothioneine
l-ergothioneine is a low-molecular weight natural product. Here, the different modes of chemical reactivity, as well as how they account for the reported molecular biological activities ofl-ergothioneine, are reviewed. By matching the physicochemical properties to the biological properties ofl-ergothioneine, a new perspective of the function and the mode of action of this enigmatic molecule emerges. l-ergothioneine is a low-molecular weight natural product, the chemical structure of which comprises oxygen-, nitrogen- and sulfur-containing functional groups. This givesl-ergothioneine specific physicochemical properties and ...
Source: FEBS Letters - January 19, 2022 Category: Biochemistry Authors: Jean ‐Claude Yadan Tags: Review Source Type: research

The T1 ‐tetramerisation domain of Kv1.2 rescues expression and preserves function of a truncated NaChBac sodium channel
This study investigated the influence of the cytoplasmic domain on ion channel assembly. When the C-terminal coiled-coil domain of the NaChBac bacterial sodium channel was swapped with an unrelated tetramerisation domain on the N terminus, the chimera expressed robustly in the membrane and produced stable, functional tetrameric channels. This indicates that bringing the transmembrane regions into proximity promotes NaChBac functional assembly. Cytoplasmic domains frequently promote functional assembly of multimeric ion channels. To investigate structural determinants of this process, we generated the ‘T1-chimera&rsqu...
Source: FEBS Letters - January 19, 2022 Category: Biochemistry Authors: Nazzareno D ’Avanzo, Andrew J. Miles, Andrew M. Powl, Colin G. Nichols, B.A. Wallace, Andrias O. O’Reilly Tags: Research Article Source Type: research

Lysophosphatidylcholine disrupts cell adhesion and induces anoikis in hepatocytes
Under physiological conditions, the integrin and cadherin signalling pathway-mediated microfilament network maintains the integrity of focal adhesion and adherens junctions and maintains the morphology of adherent cells. Treatment with lysophosphatidylcholine (LPC) disrupts integrin and cadherin signalling and, subsequently, induces microfilament depolymerization, leading to decreased cell –extracellular matrix adhesion and cell–cell junctions and induction of anoikis. AbstractLysophosphatidylcholine (LPC), the active metabolite of palmitate, triggers hepatocyte death by activating endoplasmic reticulum stress ...
Source: FEBS Letters - January 19, 2022 Category: Biochemistry Authors: Hao Chen, Jiarui Ma, Jin Liu, Lin Dou, Tao Shen, Huiyan Zuo, Fangzhi Xu, Li Zhao, Weiqing Tang, Yong Man, Yanyan Ma, Jian Li, Xiuqing Huang Tags: Research Article Source Type: research

An endogenous bornavirus ‐like nucleoprotein in miniopterid bats retains the RNA‐binding properties of the original viral protein
This study shows that miniopterid bats have a gene derived from the N gene of an ancient bornavirus, named miEBLN-1, which has evolved under purifying selection. Furthermore, miEBLN-1 encodes an RNA-binding protein that interacts with several cellular RNA-binding proteins, such as MOV10, with biochemical properties similar to bornaviral N proteins. Altogether, we provide strong evidence for the exaptation of miEBLN-1. AbstractEndogenous bornavirus-like nucleoprotein elements (EBLNs) are sequences derived from bornaviral N genes in vertebrate genomes. Some EBLNs have been suggested to encode functional proteins in host cell...
Source: FEBS Letters - January 19, 2022 Category: Biochemistry Authors: Yahiro Mukai, Masayuki Horie, Shohei Kojima, Junna Kawasaki, Ken Maeda, Keizo Tomonaga Tags: Research Article Source Type: research

Comparative characterization of nine novel GH51, GH54 and GH62 α‐l‐arabinofuranosidases from Penicillium subrubescens
In this study, nine of its ABFs were heterologously produced and characterized, demonstrating that the gene duplication event from which these additional genes have likely resulted was followed by functional diversification of the enzymes. α-l-Arabinofuranosidases (ABFs) are important enzymes in plant biomass degradation with a wide range of applications. The ascomycete fungusPenicillium  subrubescens has more α-l-arabinofuranosidase-encoding genes in its genome compared to other Penicillia. We characterized nine ABFs from glycoside hydrolase (GH) families GH51, GH54 and GH62 from this fungus and demonst...
Source: FEBS Letters - January 18, 2022 Category: Biochemistry Authors: Nancy Coconi Linares, Xinxin Li, Adiphol Dilokpimol, Ronald P. Vries Tags: Research Letter Source Type: research

Retraction statement: MiR ‐365b‐3p, down‐regulated in retinoblastoma, regulates cell cycle progression and apoptosis of human retinoblastoma cells by targeting PAX6
(Source: FEBS Letters)
Source: FEBS Letters - January 18, 2022 Category: Biochemistry Tags: Retraction Source Type: research

Retraction
(Source: FEBS Letters)
Source: FEBS Letters - January 18, 2022 Category: Biochemistry Tags: Retraction Source Type: research

A γ‐glutamyl hydrolase lacking the signal peptide confers susceptibility to folates/antifolates in acute lymphoblastic leukemia cells
In this study, we show that intact GGH is not indispensable for the chemosensitivity and growth of acute lymphoblastic leukemia (ALL) cells, whereas GGH lacking N-terminal signal peptide (GGH- ΔN) confers the significant drug resistance of ALL cells to the antifolates MTX and RTX. In addition, ALL cells harboring GGH- ΔN show high susceptibility to the change in folates, and glycosylation is not responsible for these phenotypes elicited by GGH- ΔN. Mechanistically, the loss of signal peptide enhances intracellular retention of GGH and its lysosomal disposition. Our findings clearly define thein vivo role ...
Source: FEBS Letters - January 18, 2022 Category: Biochemistry Authors: Shuxuan Wang, Yao Chen, Houshun Fang, Yan Xu, Ming Ding, Chunshuang Ma, Yanyan Lin, Zhiyan Cui, Huiying Sun, Qun Niu, Shuzhang Sun, Bin ‐Bing S Zhou, Ning Xiao, Hui Li Tags: Research Article Source Type: research

Overactivation of the androgen receptor exacerbates gravid uterine ferroptosis via interaction with and suppression of the NRF2 defense signaling pathway
This study shows that in polycystic ovary syndrome (PCOS), uterine ferroptotic signaling cascades are triggered, as evidenced by suppressed SLC7A11/GSH/GPX4 signaling, impaired iron metabolism, and increased lipid peroxidation, through an androgen receptor (AR)-dependent mechanism. Long-term exposure to 5 α-dihydrotestosterone (DHT) increases the interaction of the uterine AR with the transcription factor NRF2, leading to suppressed NRF2 antioxidative capacity and eventually promoting uterine ferroptosis. AbstractThe mechanisms through which the androgen-dependent activation of the androgen receptor (AR) regulates gr...
Source: FEBS Letters - January 18, 2022 Category: Biochemistry Authors: Min Hu, Yuehui Zhang, Lingjing Lu, Yu Zhou, Denghui Wu, Mats Br ännström, Linus R Shao, Håkan Billig Tags: Research Article Source Type: research

Crystal structure of the Toll/interleukin ‐1 receptor (TIR) domain of IL‐1R10 provides structural insights into TIR domain signaling
This study presents the crystal structure of the Toll/interleukin-1 receptor (TIR) domain of human interleukin-1 receptor 10 (IL-1R10), also called IL-1RAPL2. It is similar to IL-1R9TIR (IL-1RAPL1) but shows significant structural differences to TIR domains from Toll-like receptors and the adaptor proteins MAL and MyD88. We propose that the dimer observed in the IL-1R10TIR crystals represents a non-signaling, auto-inhibited form of the protein. AbstractThe Toll/interleukin-1 receptor (TIR) domains are key innate immune signaling modules. Here, we present the crystal structure of the TIR domain of human Interleukin-1 recept...
Source: FEBS Letters - January 18, 2022 Category: Biochemistry Authors: Surekha Nimma, Weixi Gu, Mohammad K. Manik, Thomas Ve, Jeffrey D. Nanson, Bostjan Kobe Tags: Research Article Source Type: research

Characterizing the amino acid activation center of the naturally editing ‐deficient aminoacyl‐tRNA synthetase PheRS in Mycoplasma mobile
This study examined the amino acid activation center of theMycoplasma mobile aminoacyl-tRNA synthetase PheRS through point mutation and enzyme kinetics. A trend ofm-Tyr (an oxidation byproduct of Phe) being poorly discriminated during the step of activation was observed. Since MmPheRS does not editm-Tyr, these findings suggest thatM. mobile may be susceptible tom-Tyr toxicity when Phe is limited unless other quality control mechanisms exist AbstractTo ensure correct amino acids are incorporated during protein synthesis, aminoacyl-tRNA synthetases (aaRSs) employ proofreading mechanisms collectively referred to as editing. A...
Source: FEBS Letters - January 18, 2022 Category: Biochemistry Authors: Nien ‐Ching Han, Arundhati Kavoor, Michael Ibba Tags: Research Letter Source Type: research

Upstream charged and hydrophobic residues impact the timing of membrane insertion of transmembrane helices
During cotranslational membrane insertion, transmembrane helices first make contact with the membrane when their N-terminal end is ~45 residues away from the peptidyl transferase center. Here, we show that upstream positively charged and re-entrant loops in theEscherichia coli inner membrane protein BtuC can delay the first contact. Thus, both electrostatic and hydrophobic interactions involving upstream sequence elements can impact membrane insertion AbstractDuring SecYEG-mediated cotranslational insertion of membrane proteins, transmembrane helices (TMHs) first make contact with the membrane when their N-terminal end is ...
Source: FEBS Letters - January 18, 2022 Category: Biochemistry Authors: Felix Nicolaus, Fatima Ibrahimi, Anne den Besten, Gunnar von Heijne Tags: Research Letter Source Type: research

Phenylalanine stacking enhances the red fluorescence of biliverdin IX α on UV excitation in sandercyanin fluorescent protein
On UV excitation, free biliverdin IX α (BV) shows blue fluorescence and negligible emission in red. But when bound to Sandercyanin (SFP), enhanced red emission is observed, and blue fluorescence disappears. Phenylalanine stacking to BV plays a crucial role in the conformational selection of BV. It stabilizes the lowest excited state r esulting in enhanced red fluorescence of the SFP-BV complex. Biliverdin IX α (BV) binds to several prokaryotic and eukaryotic proteins. How nature exploits the versatility of BV's properties is not fully understood. Unlike free BV, the Sandercyanin fluorescent protein bound to BV ...
Source: FEBS Letters - January 17, 2022 Category: Biochemistry Authors: Keerti Yadav, Swagatha Ghosh, Arvind Barak, Wayne Schaefer, Ramaswamy Subramanian Tags: Research Letter Source Type: research

NADH/NAD+ binding and linked tetrameric assembly of the oncogenic transcription factors CtBP1 and CtBP2
This study presents biophysical analysis of this process revealing that high-affinity NAD(H) binding triggers assembly of both CtBP1 and CtBP2 into tetramers. These findings provide key insight for the development of CtBP-specific antineoplastic agents. The activation of oncogenic C-terminal binding Protein (CtBP) transcriptional activity is coupled with NAD(H) binding and homo-oligomeric assembly, although the level of CtBP assembly and nucleotide binding affinity continues to be debated. Here, we apply biophysical techniques to address these fundamental issues for CtBP1 and CtBP2. Our ultracentrifugation results unambigu...
Source: FEBS Letters - January 17, 2022 Category: Biochemistry Authors: Heidi Erlandsen, Anne M. Jecrois, Jeffry C. Nichols, James L. Cole, William E. Royer Tags: Research Letter Source Type: research

Aspirin damages the cell wall of Saccharomyces cerevisiae by inhibiting the expression and activity of dolichol ‐phosphate mannose synthase 1
This study shows that aspirin can cause cell wall damage inSaccharomyces cerevisiae by interfering with dolichol phosphate mannose synthase 1 (DPM1) expression and enzyme activity, leading to the inhibition ofS. cerevisiae cell growth. Additionally, the inhibitory effect of aspirin on DPM1 is conserved inCandida albicans. Our findings indicate that DPM1 is a potential target for antifungal drug development. AbstractAspirin is a commonly used anti-inflammatory, analgesic, and antithrombotic drug. It has attracted attention due to its potential antifungal therapeutic effect; however, the molecular mechanism is poorly underst...
Source: FEBS Letters - January 14, 2022 Category: Biochemistry Authors: Ming Li, Pan Zhu, Zhiwei Huang, Yunxia Huang, Xiaoguang Lv, Qiaoqiao Zheng, Ziting Zhu, Zheyu Fan, Youjun Yang, Ping Shi Tags: Research Article Source Type: research

Thermodynamic and biophysical study of fatty acid effector binding to soybean lipoxygenase: implications for allostery driven by helix α2 dynamics
In this study, we examine the binding therm odynamics of the fatty acid mimic, oleyl sulfate (OS), with the monomeric model plant 15-LOX, soybean lipoxygenase (SLO), using isothermal titration calorimetry. Dynamic light scattering and differential scanning calorimetry rule out OS-induced oligomerization or structural changes. These data provi de evidence that the fatty acid allosteric regulation of SLO is controlled by the dynamics of helix α2. (Source: FEBS Letters)
Source: FEBS Letters - January 13, 2022 Category: Biochemistry Authors: Daniella E. Roberts, Amy M. Benton, Claire Fabian ‐Bayola, Anne M. Spuches, Adam R. Offenbacher Tags: Communication Source Type: research