New structural insights into the multi ‐functional influenza A matrix protein 1
AbstractInfluenza A virus matrix protein 1 (M1) is the most abundant protein within virions and functions at multiple steps of the virus life cycle, including nuclear RNA export, virus particle assembly, and virus disassembly. Two recent publications have presented the first structures of full-length M1, and show that it assembles filamentsin vitro via an interface between the N- and C- terminal domains of adjacent monomers. These filaments were found to be similar to those that form the endoskeleton of assembled virions. The structures provide a molecular basis to understand the functions of M1 during the virus life cycle...
Source: FEBS Letters - September 21, 2021 Category: Biochemistry Authors: Julia Peukes, Xiaoli Xiong, John A. G. Briggs Tags: Review Article Source Type: research

Sorting nexin 6 interacts with Cullin3 and regulates programmed death ligand 1 expression
Programmed death ligand 1 (PD-L1) is critical for the ability of cancer cells to evade attacks by the host immune system. However, the molecular mechanisms controlling PD-L1 expression have not been fully understood. Here, we demonstrate that sorting nexin 6 (SNX6) is a novel regulator of PD-L1 expression. Knockdown of SNX6 in cancer cells significantly decreases PD-L1 protein levels. In contrast, loss of SNX6 does not reduce PD-L1 mRNA levels. Instead, SNX6 interacts with Cullin3, an E3 ubiquitin ligase responsible for PD-L1 ubiquitination and subsequent degradation. By binding with Cullin3, SNX6 decreases the interaction...
Source: FEBS Letters - September 20, 2021 Category: Biochemistry Authors: Chinmoy Ghosh, Yanli Xing, Suhua Li, Rosalie G. Hoyle, Ming Sun, Jiong Li, Yue Sun Tags: Research Article Source Type: research

Transcription factor SOX2 contributes to nonalcoholic fatty liver disease development by regulating the expression of the fatty acid transporter CD36
ABSTRACTNonalcoholic fatty liver disease (NAFLD) can lead to hepatocellular carcinoma (HCC). The level of the transcription factor SOX2 correlates with HCC progression, but its role in fat accumulation remains unclear. Here, a high-fat diet, with and without fructose, significantly upregulated SOX2 in murine liver tissue. Treatment with free fatty acids (FFAs) and fructose upregulated SOX2 in murine FL83B hepatocytes. SOX2 overexpression or knockdown regulated triglyceride synthesis and lipid accumulation after FFA stimulation. CD36, a fatty acid transporter, and Yes-associated protein (YAP), a downstream molecule of the H...
Source: FEBS Letters - September 18, 2021 Category: Biochemistry Authors: Chen Shen, Jin Hong Chen, Ha Ram Oh, Ji Hyun Park Tags: Research Letter Source Type: research

The circadian clock and diseases of the skin
AbstractOrganisms have an evolutionarily conserved internal rhythm that helps them anticipate and adapt to daily changes in the environment. Synchronized to the light-dark cycle with a period of around 24 hours, the timing of the circadian clock is set by light-triggering signals sent from the retina to the suprachiasmatic nucleus. Other inputs, including food intake, exercise, and temperature, also affect clocks in peripheral tissues, including skin. Here, we review the intricate interplay between the core clock network and fundamental physiological processes in skin such as homeostasis, regeneration, immune and stress re...
Source: FEBS Letters - September 18, 2021 Category: Biochemistry Authors: Junyan Duan, Elyse Noelani Greenberg, Satya Swaroop Karri, Bogi Andersen Tags: Review Source Type: research

Front Cover
Cover illustrationIn the process of macroautophagy, both autophagic bodies and lipophagic vesicles are observed in the yeast vacuole. Freeze-fracture electron microscopy reveals that phosphatidylinositol 3-phosphate (PtdIns(3)P) is localized in the luminal leaflet of autophagic body membrane (yellow) and in the cytoplasmic leaflet of lipophagic vesicle membrane (pink), whereas the labeling of PtdIns(3)P is not detected in the cytoplasmic leaflet of autophagic body membrane (blue). The cover image refers to the article “Selective increment of phosphatidylserine on the autophagic body membrane in the yeast vacuole&rdqu...
Source: FEBS Letters - September 13, 2021 Category: Biochemistry Tags: Issue Information Source Type: research

Pseudouridines in RNAs: switching atoms means shifting paradigms
The structure, stability, and function of various coding and noncoding RNAs are influenced by chemical modifications. Pseudouridine ( Ψ) is one of the most abundant post-transcriptional RNA base modifications and has been detected at individual positions in tRNAs, rRNAs, mRNAs, and snRNAs, which are referred to as Ψ-sites. By allowing formation of additional bonds with neighboring atoms, Ψ strengthens RNA–RNA and RNA–protei n interactions. Although many aspects of the underlying modification reactions remain unclear, the advent of new transcriptome-wide methods to quantitatively detect Ψ-sites h...
Source: FEBS Letters - September 13, 2021 Category: Biochemistry Authors: Ting ‐Yu Lin, Rahul Mehta, Sebastian Glatt Tags: Review Article Source Type: research

Sorting Nexin 6 Interacts with Cullin3 and Regulates Programmed Death ‐ligand 1 Expression
AbstractProgrammed death-ligand 1 (PD-L1) is critical for the ability of cancer cells to evade attacks by the host immune system. However, the molecular mechanisms controlling PD-L1 expression have not been fully understood. Here, we demonstrate that sorting nexin 6 (SNX6) is a novel regulator of PD-L1 expression. Knockdown of SNX6 in cancer cells significantly decreases PD-L1 protein levels. In contrast, loss of SNX6 does not reduce PD-L1 mRNA levels. Instead, SNX6 interacts with Cullin3, an E3 ubiquitin ligase responsible for PD-L1 ubiquitination and subsequent degradation. By binding with Cullin3, SNX6 decreases the int...
Source: FEBS Letters - September 13, 2021 Category: Biochemistry Authors: Chinmoy Ghosh, Yanli Xing, Suhua Li, Rosalie G. Hoyle, Ming Sun, Jiong Li, Yue Sun Tags: RESEARCH ARTICLE Source Type: research

AKT controls NLRP3 inflammasome activation by inducing DDX3X phosphorylation
The NLRP3 inflammasome, a critical component of the innate immune system, induces caspase-1 activation and interleukin-1 β maturation and drives cell fate toward pyroptosis. However, the mechanism of NLRP3 inflammasome activation still remains elusive. Here we provide evidence that AKT regulates NLRP3 inflammasome activation. Upon NLRP3 activation, AKT activity is inhibited by second stimulus-induced reactive oxygen species. In contrast, AKT activation leads to NLRP3 inhibition and improved mitochondrial fitness. Mechanistically, AKT induces the phosphorylation of the DDX3X (DEAD-box helicase 3, X-linked), a recently ...
Source: FEBS Letters - September 11, 2021 Category: Biochemistry Authors: Xingchen Guo, Sheng Chen, Weiwei Yu, Zhexu Chi, Zhen Wang, Ting Xu, Jian Zhang, Danlu Jiang, Yuxian Guo, Hui Fang, Kailian Zhang, Mobai Li, Dehang Yang, Qianzhou Yu, Qizhen Ye, Di Wang, Xue Zhang, Yingliang Wu Tags: Research Article Source Type: research

Non ‐negative blind deconvolution for signal processing in a CRISPR‐edited iPSC‐cardiomyocyte model of dilated cardiomyopathy
We report a non-negative blind deconvolution (NNBD) approach to quantify calcium (Ca2+) handling, beating force, and contractility in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) at the single-cell level. We employed CRISPR/Cas gene editing to introduce a dilated cardiomyopathy (DCM)-causing mutation in troponin T (TnT), TnT-R141W, into wildtype control iPSCs (MUT). The NNDB-based method enabled data parametrization, fitting, and analysis in wildtype controls versus isogenic MUT iPSC-CMs. Of note, Cas9-edited TnT-R141W iPSC-CMs revealed significantly reduced beating force and prolonged contractile ...
Source: FEBS Letters - September 6, 2021 Category: Biochemistry Authors: Hang Xu, Ruheen Wali, Cleophas Cheruiyot, Jonathan Bodenschatz, Gerd Hasenfuss, Andreas Janshoff, Michael Habeck, Antje Ebert Tags: RESEARCH LETTER Source Type: research

Genome ‐scale metabolic modelling of SARS‐CoV‐2 in cancer cells reveals an increased shift to glycolytic energy production
We present a genome-scale map of short-term metabolic alterations triggered by SARS-CoV-2 infection of cancer cells. Through transcriptomic- and proteomic-informed genome-scale metabolic modelling, we characterise the role of RNA and fatty acid biosynthesis in conjunction with a rewiring in energy production pathways and enhanced cytokine secretion. These findings link together complementary aspects of viral invasion of cancer cells, while providing mechanistic insights that can inform the development of treatment strategies. (Source: FEBS Letters)
Source: FEBS Letters - September 5, 2021 Category: Biochemistry Authors: Elisabeth Yaneske, Guido Zampieri, Loris Bertoldi, Giuseppe Benvenuto, Claudio Angione Tags: Research Letter Source Type: research

Proline ‐rich extensin‐like receptor kinases PERK5 and PERK12 are involved in pollen tube growth
Proline-rich extensin-like receptor kinases (PERKs) belong to the hydroxyproline-rich glycoprotein (HRGP) superfamily known to be involved in many plant developmental processes. Here, we characterized two pollen-expressedPERKs fromArabidopsis  thaliana,PERK5 andPERK12. Pollen tube growth was impaired in single and doubleperk5-1 perk12-1 loss of function mutants, with an impact on seed production. When the segregation was analysed, a male gametophytic defect was found, indicating thatperk5-1 andperk12-1 mutants carry deficient pollen transmission. Furthermore,perk5-1 perk12-1 displayed an excessive accumulation of pect...
Source: FEBS Letters - September 5, 2021 Category: Biochemistry Authors: Cecilia Borassi, Ana R. Sede, Mart ín A. Mecchia, Silvina Mangano, Eliana Marzol, Silvina P. Denita‐Juarez, Juan D. Salgado Salter, Silvia M. Velasquez, Jorge P. Muschietti, José M. Estevez Tags: Research Letter Source Type: research

Synergistic activation of thrombin and angiotensin II receptors revealed by bioluminescence resonance energy transfer
We recently reported a physical interaction between the angiotensin II (AngII) receptor (AT1R) and thrombin receptor (PAR1) in HEK293 cells using bioluminescence resonance energy transfer (BRET) technology. This was characterized by thrombin trans-activating AT1R and the synergistic responses of the AT1R –PAR1 complex. Here, we investigated the other face of the coin by examining the effect of AT1R on PAR1 activity using BRET. AngII/AT1R did not promote PAR1 activation in the absence of thrombin. However, the combination of thrombin and AngII resulted in their synergistic/allosteric action. Moreov er, AngII/AT1R pote...
Source: FEBS Letters - September 2, 2021 Category: Biochemistry Authors: Isra Al Zamel, Abdulrasheed Palakkott, Mohammed Akli Ayoub Tags: Research Letter Source Type: research

Pseudouridines in RNAs – switching atoms means shifting paradigms
AbstractThe structure, stability and function of various coding and non-coding RNAs are influenced by chemical modifications. Pseudouridine ( Ψ) is one of the most abundant post-transcriptional RNA base modifications and has been detected at individual positions in tRNAs, rRNAs, mRNAs and snRNAs, which are referred to as Ψ-sites. By allowing formation of additional bonds with neighboring atoms, Ψ strengthens RNA-RNA and RNA-protein int eractions. Although many aspects of the underlying modification reactions remain unclear, the advent of new transcriptome-wide methods to quantitatively detect Ψ-sites has re...
Source: FEBS Letters - September 1, 2021 Category: Biochemistry Authors: Ting ‐Yu Lin, Rahul Mehta, Sebastian Glatt Tags: REVIEW Source Type: research

Azurocidin is loaded into small extracellular vesicles via its N ‐linked glycosylation and promotes intravasation of renal cell carcinoma cells
Azurocidin (AZU1) is an antimicrobial protein secreted by neutrophils that acts as a chemoattractant for monocytes and macrophages and a permeabilizer of vascular endothelial cells. We previously identified AZU1 to be specifically present in extracellular vesicles (EVs) obtained from renal cell carcinoma (RCC) tissues. Here, we examined the relationship between N-linked glycosylation and AZU1 loading into small EVs (SEVs). Inhibition of N-linked glycosylation by introducing mutations in three glycosylation sites inhibited AZU1 loading into SEVs. Furthermore, SEVs released from AZU1-wild-type cells increased the Ca2+ concen...
Source: FEBS Letters - September 1, 2021 Category: Biochemistry Authors: Takuya Naito, Kentaro Jingushi, Koji Ueda, Kazutake Tsujikawa Tags: Research Article Source Type: research

Interface ‐based design of the favipiravir‐binding site in SARS‐CoV‐2 RNA‐dependent RNA polymerase reveals mutations conferring resistance to chain termination
Favipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19. Accumulation of mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RdRp may facilitate antigenic drift, generating favipiravir resistance. Focussing on the chain-termination mechanism utilized by favipiravir, we used high-throughput interface-based protein design to generate>  100 000 designs of the favipiravir-binding site of RdRp and identify mutational hotspots. We identified several single-point mutants and designs having a sequence identity of 97%–98%...
Source: FEBS Letters - September 1, 2021 Category: Biochemistry Authors: Aditya K. Padhi, Jagneshwar Dandapat, Prakash Saudagar, Vladimir N. Uversky, Timir Tripathi Tags: Research Article Source Type: research

Pseudouridines in RNAs – switching atoms means shifting paradigms
AbstractThe structure, stability and function of various coding and non-coding RNAs are influenced by chemical modifications. Pseudouridine ( Ψ) is one of the most abundant post-transcriptional RNA base modifications and has been detected at individual positions in tRNAs, rRNAs, mRNAs and snRNAs, which are referred to as Ψ-sites. By allowing formation of additional bonds with neighboring atoms, Ψ strengthens RNA-RNA and RNA-protein int eractions. Although many aspects of the underlying modification reactions remain unclear, the advent of new transcriptome-wide methods to quantitatively detect Ψ-sites has re...
Source: FEBS Letters - September 1, 2021 Category: Biochemistry Authors: Ting ‐Yu Lin, Rahul Mehta, Sebastian Glatt Tags: REVIEW ARTICLE Source Type: research

K+ regulates relocation of Pellino ‐2 to the site of NLRP3 inflammasome activation in macrophages
We examined the intracellular localization of human Pellino-2 in THP1-derived macrophages during activation with LPS and ATP. We observed that Pellino-2 changed intracellular localization and colocalized with the inflammasome proteins NLRP3 and ASC late in the assembly of the inflammasome. Colocalization with NLRP3 and ASC was also seen in cells maintained in potassium-free medium. The colocalization and inflammasome activation were abrogated by several potassium channel inhibitors, supporting a role for potassium efflux in modulating intracellular localization of Pellino-2. The data suggest that Pellino-2 is essential for...
Source: FEBS Letters - September 1, 2021 Category: Biochemistry Authors: Ileana Cristea, Ove Bruland, Eyvind R ødahl, Cecilie Bredrup Tags: Research Letter Source Type: research

The APC10 subunit of the anaphase ‐promoting complex/cyclosome orchestrates NLRP3 inflammasome activation during the cell cycle
This study reveals a distinct mechanism by which APC10 serves as a switch for NLRP3 inflammasome activation during the cell cycle. (Source: FEBS Letters)
Source: FEBS Letters - August 30, 2021 Category: Biochemistry Authors: Siyu Huang, Pin Wan, Shanyu Huang, Siyu Liu, Qi Xiang, Ge Yang, Muhammad Adnan Shereen, Pan Pan, Jun Wang, Weiyong Liu, Kailang Wu, Jianguo Wu Tags: Research Article Source Type: research

Tartrate ‐resistant acid phosphatase type 5/ACP5 promotes cell cycle entry of 3T3‐L1 preadipocytes by increasing IGF‐1/Akt signaling
In conclusion, TRAP 5a increases proliferation of preadipocytes in a dose-dependent fashion by promoting entry into S-phase. Part of this effect is likely due to increased IGF-1 signaling through the Akt signaling pathway. (Source: FEBS Letters)
Source: FEBS Letters - August 30, 2021 Category: Biochemistry Authors: Pernilla L ång, Christina Patlaka, Göran Andersson Tags: Research Letter Source Type: research

Targeting the non ‐ATP‐binding pocket of the MAP kinase p38γ mediates a novel mechanism of cytotoxicity in cutaneous T‐cell lymphoma (CTCL)
We describe here for the first time a lipid-binding-domain (LBD) in p38 γ mitogen-activated protein kinase (MAPK) involved in the response of T cells to a newly identified inhibitor, CSH71. We describe how CSH71, which binds to both the LBD and the ATP-binding pocket of p38γ, is selectively cytotoxic to CTCL Hut78 cells but spares normal healthy peripheral blood monon uclear (PBMC) cells, and propose possible molecular mechanisms for its action. p38γ is a key player in CTCL development, and we expect that the ability to regulate its expression by specifically targeting the lipid-binding domain will have i...
Source: FEBS Letters - August 29, 2021 Category: Biochemistry Authors: Xu Hannah Zhang, Chih ‐Hong Chen, Hongzhi Li, Jack Hsiang, Xiwei Wu, Weidong Hu, David Horne, Sangkil Nam, Jack Shively, Steven T. Rosen Tags: RESEARCH ARTICLE Source Type: research

Synergistic activation of thrombin and angiotensin II receptors revealed by bioluminescence resonance energy transfer
AbstractWe recently reported a physical interaction between the angiotensin II (AngII) receptor (AT1R) and thrombin receptor (PAR1) in HEK293 cells using bioluminescence resonance energy transfer(BRET) technology. This was characterized by thrombin trans-activating AT1R and the synergistic responses of the AT1R –PAR1 complex. Here, we investigated the other face of the coin by examining the effect of AT1R on PAR1 activity using BRET. AngII/AT1R did not promote PAR1 activation in the absence of thrombin. However, the combination of thrombin and AngII resulted in their synergistic/allosteric action. Moreov er, AngII/AT...
Source: FEBS Letters - August 29, 2021 Category: Biochemistry Authors: Isra Al Zamel, Abdulrasheed Palakkott, Mohammed Akli Ayoub Tags: RESEARCH LETTER Source Type: research

Targeting the non ‐ATP‐binding pocket of the MAP kinase p38γ mediates a novel mechanism of cytotoxicity in cutaneous T‐cell lymphoma (CTCL)
We describe here for the first time a lipid-binding-domain (LBD) in p38 γ mitogen-activated protein kinase (MAPK) involved in the response of T cells to a newly identified inhibitor, CSH71. We describe how CSH71, which binds to both the LBD and the ATP-binding pocket of p38γ, is selectively cytotoxic to CTCL Hut78 cells but spares normal healthy peripheral blood monon uclear (PBMC) cells, and propose possible molecular mechanisms for its action. p38γ is a key player in CTCL development, and we expect that the ability to regulate its expression by specifically targeting the lipid-binding domain will have i...
Source: FEBS Letters - August 28, 2021 Category: Biochemistry Authors: Xu Hannah Zhang, Chih ‐Hong Chen, Hongzhi Li, Jack Hsiang, Xiwei Wu, Weidong Hu, David Horne, Sangkil Nam, Jack Shively, Steven T. Rosen Tags: RESEARCH ARTICLE Source Type: research

Analysis of nucleoid ‐associated protein‐binding regions reveals DNA structural features influencing genome organization in Mycobacterium tuberculosis
Nucleoid-associated proteins (NAPs) maintain bacterial nucleoid configuration through their architectural properties of DNA bending, wrapping, and bridging. However, the contribution of DNA structural alterations to DNA-NAP recognition at the genomic scale remains unresolved. Present work dissects the DNA sequence, shape and altered structural preferences at a genomic scale for six NAPs inMycobacterium  tuberculosis. Results suggest narrower minor groove width (MGW) and higher DNA rigidity are marked for the binding sites of EspR and Lsr2, while mIHF, MtHU and NapM have  heterogeneous DNA structural predilections...
Source: FEBS Letters - August 27, 2021 Category: Biochemistry Authors: Sharmilee Sarkar, Upalabdha Dey, Trust Boitumelo Khohliwe, Venkata Rajesh Yella, Aditya Kumar Tags: Research Article Source Type: research

Proline ‐rich Extensin‐like Receptor Kinases PERK5 and PERK12 are involved in Pollen Tube Growth
AbstractProline-richextensin-likereceptorkinases (PERKs) belong to the hydroxyproline-rich glycoprotein (HRGP) superfamily known to be involved in many plant developmental processes. Here, we characterized two pollen-expressedPERKs fromArabidopsis thaliana,PERK5 andPERK12. Pollen tube growth was impaired in single and doubleperk5-1 perk12-1 loss of function mutants, with an impact on seed production. When the segregation was analysed, a male gametophytic defect was found, indicating thatperk5-1 andperk12-1 mutants carry deficient pollen transmission. Furthermore,perk5-1 perk12-1 displayed an excessive accumulation of pecti...
Source: FEBS Letters - August 26, 2021 Category: Biochemistry Authors: Cecilia Borassi, Ana R. Sede, Mart ín A. Mecchia, Silvina Mangano, Eliana Marzol, Silvina P. Denita‐Juarez, Juan D. Salgado Salter, Silvia M. Velasquez, Jorge P. Muschietti, José M. Estevez Tags: RESEARCH LETTER Source Type: research

The SAC1 phosphatase domain of synaptojanin ‐1 is activated by interacting with polyunsaturated fatty acid‐containing phosphatidic acids
Although there are many phosphatidic acid (PA) molecular species based on its fatty acyl compositions, their interacting partners have been poorly investigated. Here, we identified synaptojanin-1 (SYNJ1), Parkinson ’s disease-related protein that is essential for regulating clathrin-mediated synaptic vesicle endocytosis via dually dephosphorylating D5 and D4 position phosphates from phosphatidylinositol (PI) (4,5)-bisphosphate, as a 1-stearoyl-2-docosahexaenoyl (18:0/22:6)-PA-binding protein. SYNJ1 failed to substantially associate with other acidic phospholipids. Although SYNJ1 interacted with 18:0/20:4-PA in additi...
Source: FEBS Letters - August 24, 2021 Category: Biochemistry Authors: Fumi Hoshino, Fumio Sakane Tags: Research Letter Source Type: research

Identification and characterization of glycosyltransferases catalyzing direct xanthone 4 ‐C‐glycosylation in Hypericum perforatum
Xanthones are compounds with a diphenyl ether skeleton mainly found in plants and often glycosylated at carbon atoms. Although manyC-glycosyltransferases (CGTs) participating in flavoneC-glycosylation have been identified, MiCGT fromMangifera  indica, adding sugar to an open-chain benzophenone skeleton, is the only identified xanthone biosynthesis-related CGT. Here, we identified two CGTs fromHypericum  perforatum that add sugar to the closed-ring xanthone, but not benzophenone. These CGTs catalyze sugar transfer to the C-4 position of norathyriol (1,3,6,7-tetrahydroxyxanthone) to form isomangiferin (1,3,6,7-tetr...
Source: FEBS Letters - August 24, 2021 Category: Biochemistry Authors: Kai Uchida, Tomoyoshi Akashi, Masami Yokota Hirai Tags: Research Letter Source Type: research

Unique structural features of the adenylate kinase hCINAP/AK6 and its multifaceted functions in carcinogenesis and tumor progression
Human coilin-interacting nuclear ATPase protein (hCINAP), also known as adenylate kinase 6 (AK6), is an atypical adenylate kinase with critical roles in many biological processes, including gene transcription, ribosome synthesis, cell metabolism, cell proliferation and apoptosis, DNA damage responses, and genome stability. Furthermore, hCINAP/AK6 dysfunction is associated with cancer and various inflammatory diseases. In this review, we summarize the structural features and biological roles of hCINAP in several important signaling pathways, as well as its connection with tumor onset and progression. (Source: FEBS Letters)
Source: FEBS Letters - August 23, 2021 Category: Biochemistry Authors: Ruidan Xu, Yongfeng Yang, Xiaofeng Zheng Tags: Review Source Type: research

Front Cover
Cover illustrationActivation of immune cells such as T-cells goes along with a massive reorganisation of molecules on the plasma membrane. To decipher these heterogeneities, the basal surface of activating T cells was imaged using spectrally resolved microscopy together with environment-sensitive membrane dyes. With spectral unmixing, maps of different spectral properties of emitted fluorescence were devised, allowing to determine the local lipid order around key membrane proteins. The cover image refers to the article “Aggregation and mobility of membrane proteins interplay with local lipid order in the plasma membr...
Source: FEBS Letters - August 23, 2021 Category: Biochemistry Tags: Issue Information Source Type: research

HutT functions as the major L ‐histidine transporter in Pseudomonas putida KT2440
Histidine is an important carbon and nitrogen source of γ-proteobacteria and can affect bacteria–host interactions. The mechanisms of histidine uptake are only partly understood. Here, we analyze functional properties of the putative histidine transporter HutT of the soil bacteriumPseudomonas  putida. ThehutT gene is part of the histidine utilization operon, and the gene product belongs to the amino acid-polyamine-organocation (APC) family of secondary transporters. Deletion ofhutT severely impairs growth ofP.  putida on histidine, suggesting that the encoded transporter is the major histidine uptake ...
Source: FEBS Letters - August 23, 2021 Category: Biochemistry Authors: Larissa Wirtz, Michelle Eder, Anna ‐Katharina Brand, Heinrich Jung Tags: Research Article Source Type: research

ADP ‐heptose enables Helicobacter pylori to exploit macrophages as a survival niche by suppressing antigen‐presenting HLA‐II expression
The persistence ofHelicobacter  pylori in the human gastric mucosa implies that the immune response fails to clear the infection. We found thatH.  pylori compromises the antigen presentation ability of macrophages, because of the decline of the presenting molecules HLA-II. Here, we reveal that the main bacterial factor responsible for this effect is ADP-heptose, an intermediate metabolite in the biosynthetic pathway of lipopolysaccharide (LPS) that elicits a pro-inflammatory response in gastric epithelial cells. In macrophages, it upregulates the expression of miR146b which, in turn, would downmodulate CIITA, the...
Source: FEBS Letters - August 23, 2021 Category: Biochemistry Authors: Sara Coletta, Greta Battaggia, Chiara Della Bella, Matteo Furlani, Martina Hauke, Larissa Faass, Mario M. D ’Elios, Christine Josenhans, Marina Bernard Tags: Research Letter Source Type: research

ASC ‐1 transporter‐dependent amino acid uptake is required for the efficient thermogenic response of human adipocytes to adrenergic stimulation
Brown and beige adipocytes dissipate energy by uncoupling protein 1 (UCP1)-dependent and UCP1-independent thermogenesis, which may be utilized to develop treatments against obesity. We have found that mRNA and protein expression of the alanine/serine/cysteine transporter-1 (ASC-1) was induced during adipocyte differentiation of human brown-prone deep neck and beige-competent subcutaneous neck progenitors, and SGBS preadipocytes. cAMP stimulation of differentiated adipocytes led to elevated uptake of serine, cysteine, and glycine, in parallel with increased oxygen consumption, augmented UCP1-dependent proton leak, increased...
Source: FEBS Letters - August 23, 2021 Category: Biochemistry Authors: Rini Arianti, Bogl árka Ágnes Vinnai, Beáta B. Tóth, Abhirup Shaw, Éva Csősz, Attila Vámos, Ferenc Győry, Pamela Fischer‐Posovszky, Martin Wabitsch, Endre Kristóf, László Fésüs Tags: Editor's Choice Source Type: research

Periostin deficiency attenuates lipopolysaccharide ‐ and obesity‐induced adipose tissue fibrosis
Periostin (POSTN) is a type of matricellular protein, but its functions in adipose fibrosis remain unclear. Here, we found that POSTN expression is significantly increased in mouse adipose tissue after treatment with lipopolysaccharide (LPS) or a high-fat diet (HFD) and that adipose progenitor cells are the main source of POSTN. In our mouse model of fibrosis,POSTN deletion protected mice from adipose fibrosis, probably through reducing the accumulation of macrophages and promoting adipocyte differentiation of progenitor cells. Taken together, our study demonstrates thatPOSTN deficiency attenuates adipose tissue fibrosis a...
Source: FEBS Letters - August 23, 2021 Category: Biochemistry Authors: Yuhan Yang, Yanfei Zhang, Xueliang Zhou, Dandan Chen, Gaoliang Ouyang, Yingfu Liu, Dan Cui Tags: Research Article Source Type: research

Aggregation and mobility of membrane proteins interplay with local lipid order in the plasma membrane of T cells
To disentangle the elusive lipid –protein interactions in T-cell activation, we investigate how externally imposed variations in mobility of key membrane proteins (T-cell receptor [TCR], kinase Lck, and phosphatase CD45) affect the local lipid order and protein colocalisation. Using spectral imaging with polarity-sensitive membra ne probes in model membranes and live Jurkat T cells, we find that partial immobilisation of proteins (including TCR) by aggregation or ligand binding changes their preference towards a more ordered lipid environment, which can recruit Lck. Our data suggest that the cellular membrane is pois...
Source: FEBS Letters - August 23, 2021 Category: Biochemistry Authors: Iztok Urban čič, Lisa Schiffelers, Edward Jenkins, Weijian Gong, Ana Mafalda Santos, Falk Schneider, Caitlin O’Brien‐Ball, Mai Tuyet Vuong, Nicole Ashman, Erdinc Sezgin, Christian Eggeling Tags: Research Article Source Type: research

Ile209 of Leishmania  donovani xanthine phosphoribosyltransferase plays a key role in determining its purine base specificity
Xanthine phosphoribosyltransferase (XPRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are purine salvaging enzymes ofLeishmania donovani with distinct 6-oxopurine specificities. LdXPRT phosphoribosylates xanthine, hypoxanthine, and guanine, with preference toward xanthine, whereas LdHGPRT phosphoribosylates only hypoxanthine and guanine. In our study, LdXPRT was used as a model to understand these purine base specificities. Mutating I209 to V, the conserved residue found in HGPRTs, reduced the affinity of LdXPRT for xanthine, converting it to an HGXPRT-like enzyme. The Y208F mutation in the active site indic...
Source: FEBS Letters - August 23, 2021 Category: Biochemistry Authors: Bhumi Patel, Dhaval Patel, Anju Pappachan Tags: Research Article Source Type: research

A cell surface ‐reducing microenvironment induces early osteogenic commitment
In this study, the correlation between mild reductant and early osteogenic commitment was evaluated. A cell surface-reducing microenvironment significantly silenced the transforming growth factor (TGF)- β signaling pathway of mesenchymal stem cells (MSCs), followed by increased focal adhesion and inhibition of cell membrane protein dimerization. Furthermore, in vivo transplantation of MSCs exposed to the reducing microenvironment resulted in an early osteogenic commitment and neobone formation. T hus, these results highlight the potential of cell surface-reducing microenvironment to influence early osteogenic com...
Source: FEBS Letters - August 23, 2021 Category: Biochemistry Authors: Hyunbum Kim, Eun ‐Seo Lee, Jiyong Kim, Hwan Drew Kim, Nathaniel S. Hwang Tags: Research Article Source Type: research

Front Cover
Cover illustrationActivation of immune cells such as T-cells goes along with a massive reorganisation of molecules on the plasma membrane. To decipher these heterogeneities, the basal surface of activating T cells was imaged using spectrally resolved microscopy together with environment-sensitive membrane dyes. With spectral unmixing, maps of different spectral properties of emitted fluorescence were devised, allowing to determine the local lipid order around key membrane proteins. The cover image refers to the article “Aggregation and mobility of membrane proteins interplay with local lipid order in the plasma membr...
Source: FEBS Letters - August 23, 2021 Category: Biochemistry Tags: Issue Information Source Type: research

Single ‐dose immunisation with a multimerised SARS‐CoV‐2 receptor binding domain (RBD) induces an enhanced and protective response in mice
Preparation and quality control of coupled antigen –Dps complexes (Ag-S-Dps). (A) SDS/PAGE of the three expressed and purified antigens as introduced in Fig. 1C, Coomassie stained. Glycosylation of Spike leads to a fuzzy appearance of its band. RBD-SpyT2 and Spike-SpyT2 were expressed in mammalian cells, and SpyT2-NP was expressed in bacteria, as was the SpyC-Dps scaffold. (B) Size exclusion chromatography to separate excess antigens after the SpyCatcher/Spytag2 coupling reactions; Superose 6 Increase in PBS. (C) SDS/PAGE of the coupled and purified Ag-S-Dps complexes. ‘RT’, no heating; ‘99&rsq...
Source: FEBS Letters - August 22, 2021 Category: Biochemistry Authors: Ralf Salzer, Jordan J. Clark, Marina Vaysburd, Veronica T. Chang, Anna Albecka, Leo Kiss, Parul Sharma, Andres Gonzalez Llamazares, Anja Kipar, Julian A. Hiscox, Andrew Owen, A. Radu Aricescu, James P. Stewart, Leo C. James, Jan L öwe Tags: Research Letter Source Type: research

Azurocidin is loaded into small extracellular vesicles via its N ‐linked glycosylation and promotes intravasation of renal cell carcinoma cells
AbstractAzurocidin (AZU1) is an antimicrobial protein secreted by neutrophils that acts as a chemoattractant for monocytes and macrophages and a permeabilizer of vascular endothelial cells. We previously identified AZU1 to be specifically present in extracellular vesicles (EVs) obtained from renal cell carcinoma (RCC) tissues. Here, we examined the relationship between N-linked glycosylation and AZU1 loading into small EVs (SEVs). Inhibition of N-linked glycosylation by introducing mutations in three glycosylation sites inhibited AZU1 loading into SEVs. Furthermore, SEVs released from AZU1- wild-type cells increased the Ca...
Source: FEBS Letters - August 21, 2021 Category: Biochemistry Authors: Takuya Naito, Kentaro Jingushi, Koji Ueda, Kazutake Tsujikawa Tags: RESEARCH ARTICLE Source Type: research

Tartrate ‐resistant acid phosphatase type 5/ACP5 promotes cell cycle entry of 3T3‐L1 pre‐adipocytes by increasing IGF‐1/Akt signaling
In conclusion, TRAP 5a increases proliferation of pre-adipocytes in a dose-dependent fashion by promoting entry into S-phase. Part of this effect is likely due to increased IGF-1 signaling through the Akt signaling pathway. (Source: FEBS Letters)
Source: FEBS Letters - August 21, 2021 Category: Biochemistry Authors: Pernilla L ång, Christina Patlaka, Göran Andersson Tags: RESEARCH LETTER Source Type: research

An updated classification and mechanistic insights into ligand binding of the substrate ‐binding proteins
In this study, the list of SBPs belonging to different clusters was updated (764 SBPs) compared to the previously reported study (504 SBPs). Furthermore, a new cluster referred to as cluster H was identified. Results reveal that SBPs follow different ligand-binding mechanisms. Intriguingly, the majority of the SBPs follow the ‘one domain movement’ rather than the well-known ‘Venus Fly-trap’ mechanism. Moreover, SBPs of a few clusters display subdomain conformational movement rather than the complete movement of the N- and C-terminal domains. (Source: FEBS Letters)
Source: FEBS Letters - August 20, 2021 Category: Biochemistry Authors: Monika Chandravanshi, Sisir Kant Tripathi, Shankar Prasad Kanaujia Tags: Communication Source Type: research

Interface ‐based design of the favipiravir‐binding site in SARS‐CoV‐2 RNA‐dependent RNA polymerase reveals mutations conferring resistance to chain termination
AbstractFavipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19. Accumulation of mutations in SARS-CoV-2 RdRp may facilitate antigenic drift, generating favipiravir resistance.  Focusing on the chain-termination mechanism utilized by favipiravir, we used high-throughput interface-based protein design to generate>100,000 designs  of the favipiravir-binding site of RdRp and identify mutational hotspots. We identified several single-point mutants and designs having a sequence identity of 97–98% with wildtype...
Source: FEBS Letters - August 19, 2021 Category: Biochemistry Authors: Aditya K. Padhi, Jagneshwar Dandapat, Prakash Saudagar, Vladimir N. Uversky, Timir Tripathi Tags: RESEARCH ARTICLE Source Type: research

Genome ‐scale metabolic modelling of SARS‐CoV‐2 in cancer cells reveals an increased shift to glycolytic energy production
We present a genome-scale map of short-term metabolic alterations triggered by SARS-CoV-2 infection of cancer cells. Through transcriptomics- and proteomics-informed genomescale metabolic modelling, we characterise the role of RNA and fatty acid biosynthesis in conjunction with a rewiring in energy production pathways and enhanced cytokine secretion. These findings link together complementary aspects of viral invasion of cancer cells, while providing mechanistic insights that can inform the development of treatment strategies. (Source: FEBS Letters)
Source: FEBS Letters - August 19, 2021 Category: Biochemistry Authors: Elisabeth Yaneske, Guido Zampieri, Loris Bertoldi, Giuseppe Benvenuto, Claudio Angione Tags: RESEARCH LETTER Source Type: research

The APC10 subunit of the anaphase ‐promoting complex/cyclosome orchestrates NLRP3 inflammasome activation during the cell cycle
This study reveals a distinct mechanism by which APC10 serves as a switch for NLRP3 inflammasome activation during the cell cycle. (Source: FEBS Letters)
Source: FEBS Letters - August 18, 2021 Category: Biochemistry Authors: Siyu Huang, Pin Wan, Shanyu Huang, Liu Siyu, Qi Xiang, Ge Yang, Muhammad Adnan Shereen, Pan Pan, Jun Wang, Weiyong Liu, Kailang Wu, Jianguo Wu Tags: RESEARCH ARTICLE Source Type: research

A glycosaminoglycan microarray identifies the binding of SARS ‐CoV‐2 spike protein to chondroitin sulfate E
In this study, we developed GAG microarrays based on fluorescence detection for high-sensitivity screening of the GAG-binding specificity of proteins and applied it for the analysis of SARS-CoV-2 spike (S) protein. Among the 20 distinct GAGs, the S protein bound not only to heparin (HEP)/HS but also to chondroitin sulfate E (CSE) in a concentration-dependent manner. We then analyzed the specificity of each subunit of the S protein. While the S1 subunit showed exclusive binding to HEP, the S2 subunit also bound to CSE and HEP/HS. CSE might act as an alternative attachment factor for HS in SARS-CoV-2 infection. (Source: FEBS Letters)
Source: FEBS Letters - August 18, 2021 Category: Biochemistry Authors: Tomoko Watanabe, Ko Takeda, Keiko Hiemori, Toshikazu Minamisawa, Hiroaki Tateno Tags: Research Letter Source Type: research