FEBS LettersPub Date : 2021-08-01Epub Date: 2021-07-07DOI: 10.1002/1873-3468.14153
Iztok Urbančič, Lisa Schiffelers, Edward Jenkins, Weijian Gong, Ana Mafalda Santos, Falk Schneider, Caitlin O'Brien-Ball, Mai Tuyet Vuong, Nicole Ashman, Erdinc Sezgin, Christian Eggeling
{"title":"Aggregation and mobility of membrane proteins interplay with local lipid order in the plasma membrane of T cells.","authors":"Iztok Urbančič, Lisa Schiffelers, Edward Jenkins, Weijian Gong, Ana Mafalda Santos, Falk Schneider, Caitlin O'Brien-Ball, Mai Tuyet Vuong, Nicole Ashman, Erdinc Sezgin, Christian Eggeling","doi":"10.1002/1873-3468.14153","DOIUrl":"10.1002/1873-3468.14153","url":null,"abstract":"<p><p>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 membrane 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 poised to modulate the frequency of protein encounters upon alterations of their mobility, for example in ligand binding, which offers new mechanistic insight into the involvement of lipid-mediated interactions in membrane-hosted signalling events.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"595 16","pages":"2127-2146"},"PeriodicalIF":3.0,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39018058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2021-08-01Epub Date: 2021-07-23DOI: 10.1002/1873-3468.14155
Rini Arianti, Boglárka Ágnes Vinnai, Beáta B Tóth, Abhirup Shaw, Éva Csősz, Attila Vámos, Ferenc Győry, Pamela Fischer-Posovszky, Martin Wabitsch, Endre Kristóf, László Fésüs
{"title":"ASC-1 transporter-dependent amino acid uptake is required for the efficient thermogenic response of human adipocytes to adrenergic stimulation.","authors":"Rini Arianti, Boglárka Ágnes Vinnai, Beáta B Tóth, Abhirup Shaw, Éva Csősz, Attila Vámos, Ferenc Győry, Pamela Fischer-Posovszky, Martin Wabitsch, Endre Kristóf, László Fésüs","doi":"10.1002/1873-3468.14155","DOIUrl":"10.1002/1873-3468.14155","url":null,"abstract":"<p><p>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 creatine-driven substrate cycle-coupled respiration, and upregulation of thermogenesis marker genes and several respiratory complex subunits; these outcomes were impeded in the presence of the specific ASC-1 inhibitor, BMS-466442. Our data suggest that ASC-1-dependent consumption of serine, cysteine, and glycine is required for efficient thermogenic stimulation of human adipocytes.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"595 16","pages":"2085-2098"},"PeriodicalIF":3.0,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39150599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2021-08-01Epub Date: 2021-07-03DOI: 10.1002/1873-3468.14154
Yuhan Yang, Yanfei Zhang, Xueliang Zhou, Dandan Chen, Gaoliang Ouyang, Yingfu Liu, Dan Cui
{"title":"Periostin deficiency attenuates lipopolysaccharide- and obesity-induced adipose tissue fibrosis.","authors":"Yuhan Yang, Yanfei Zhang, Xueliang Zhou, Dandan Chen, Gaoliang Ouyang, Yingfu Liu, Dan Cui","doi":"10.1002/1873-3468.14154","DOIUrl":"10.1002/1873-3468.14154","url":null,"abstract":"<p><p>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 that POSTN deficiency attenuates adipose tissue fibrosis and improves insulin resistance, providing new insights into the diagnosis and treatment of type II diabetes by targeting adipose tissue fibrosis.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"595 16","pages":"2099-2112"},"PeriodicalIF":3.0,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39103532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Conformational changes in the nucleotide-binding domains of P-glycoprotein induced by ATP hydrolysis.","authors":"Sepehr Dehghani-Ghahnaviyeh, Karan Kapoor, Emad Tajkhorshid","doi":"10.1002/1873-3468.13992","DOIUrl":"https://doi.org/10.1002/1873-3468.13992","url":null,"abstract":"<p><p>P-glycoprotein (Pgp) is a member of the ABC transporter superfamily with high physiological importance. Pgp nucleotide-binding domains (NBDs) drive the transport cycle through ATP binding and hydrolysis. We use molecular dynamics simulations to investigate the ATP hydrolysis-induced conformational changes in NBDs. Five systems, including all possible ATP/ADP combinations in the NBDs and the APO system, are simulated. ATP/ADP exchange induces conformational changes mostly within the conserved signature motif of the NBDs, resulting in relative orientational changes in the NBDs. Nucleotide removal leads to additional orientational changes in the NBDs, allowing their dissociation. Furthermore, we capture putative hydrolysis-competent configurations in which the conserved glutamate in the Walker-B motif acts as a catalytic base capturing a water molecule likely initiating ATP hydrolysis.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"595 6","pages":"735-749"},"PeriodicalIF":3.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13992","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38575298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ABCB1/MDR1/P-gp employs an ATP-dependent twist-and-squeeze mechanism to export hydrophobic drugs.","authors":"Atsushi Kodan, Ryota Futamata, Yasuhisa Kimura, Noriyuki Kioka, Toru Nakatsu, Hiroaki Kato, Kazumitsu Ueda","doi":"10.1002/1873-3468.14018","DOIUrl":"https://doi.org/10.1002/1873-3468.14018","url":null,"abstract":"<p><p>ABCB1, also called MDR1 or P-glycoprotein, exports various hydrophobic compounds and plays an essential role as a protective physiological barrier in several organs, including the brain, testis, and placenta. However, little is known about the structural mechanisms that allow ABCB1 to recognize hydrophobic compounds of diverse structures or the coupling of ATP hydrolysis to uphill substrate export. High-resolution X-ray crystal structures of the pre- and post-transport states and FRET analyses in living cells have revealed that an aromatic hydrophobic network at the top of the inner cavity is key for the conformational change in ABCB1 that is triggered by a hydrophobic substrate. ATP binding, but not hydrolysis, induces a progressive network that results in a twisting motion of the whole protein, squeezing out the substrate directly to the extracellular space. This twist-and-squeeze mechanism by which ABCB1 exports hydrophobic substrates is distinct from those of other transporters.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"595 6","pages":"707-716"},"PeriodicalIF":3.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.14018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38673033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2021-03-01Epub Date: 2020-12-04DOI: 10.1002/1873-3468.13984
Corentin R Fostier, Laura Monlezun, Farès Ousalem, Shikha Singh, John F Hunt, Grégory Boël
{"title":"ABC-F translation factors: from antibiotic resistance to immune response.","authors":"Corentin R Fostier, Laura Monlezun, Farès Ousalem, Shikha Singh, John F Hunt, Grégory Boël","doi":"10.1002/1873-3468.13984","DOIUrl":"https://doi.org/10.1002/1873-3468.13984","url":null,"abstract":"<p><p>Energy-dependent translational throttle A (EttA) from Escherichia coli is a paradigmatic ABC-F protein that controls the first step in polypeptide elongation on the ribosome according to the cellular energy status. Biochemical and structural studies have established that ABC-F proteins generally function as translation factors that modulate the conformation of the peptidyl transferase center upon binding to the ribosomal tRNA exit site. These factors, present in both prokaryotes and eukaryotes but not in archaea, use related molecular mechanisms to modulate protein synthesis for heterogenous purposes, ranging from antibiotic resistance and rescue of stalled ribosomes to modulation of the mammalian immune response. Here, we review the canonical studies characterizing the phylogeny, regulation, ribosome interactions, and mechanisms of action of the bacterial ABC-F proteins, and discuss the implications of these studies for the molecular function of eukaryotic ABC-F proteins, including the three human family members.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"595 6","pages":"675-706"},"PeriodicalIF":3.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.13984","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38562107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2021-03-01Epub Date: 2021-01-06DOI: 10.1002/1873-3468.14026
Konstantinos Tassis, Ruslan Vietrov, Matthijs de Koning, Marijn de Boer, Giorgos Gouridis, Thorben Cordes
{"title":"Single-molecule studies of conformational states and dynamics in the ABC importer OpuA.","authors":"Konstantinos Tassis, Ruslan Vietrov, Matthijs de Koning, Marijn de Boer, Giorgos Gouridis, Thorben Cordes","doi":"10.1002/1873-3468.14026","DOIUrl":"https://doi.org/10.1002/1873-3468.14026","url":null,"abstract":"<p><p>The current model of active transport via ABC importers is mostly based on structural, biochemical and genetic data. We here establish single-molecule Förster resonance energy transfer (smFRET) assays to monitor the conformational states and heterogeneity of the osmoregulatory type I ABC importer OpuA from Lactococcus lactis. We present data probing both intradomain distances that elucidate conformational changes within the substrate-binding domain (SBD) OpuAC, and interdomain distances between SBDs or transmembrane domains. Using this methodology, we studied ligand-binding mechanisms, as well as ATP and glycine betaine dependences of conformational changes. Our work expands the scope of smFRET investigations towards a class of so far unstudied ABC importers, and paves the way for a full understanding of their transport cycle in the future.</p>","PeriodicalId":50454,"journal":{"name":"FEBS Letters","volume":"595 6","pages":"717-734"},"PeriodicalIF":3.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1873-3468.14026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38706350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}