The FEBS journal最新文献_第4页

Structural basis of Ebp pilus shaft formation and anchoring in vancomycin-resistant Enterococci. 耐万古霉素肠球菌Ebp菌毛轴形成和锚定的结构基础。

The FEBS journal Pub Date : 2025-07-03 DOI: 10.1111/febs.70173

Vinay Sharma, Vengadesan Krishnan

{"title":"Structural basis of Ebp pilus shaft formation and anchoring in vancomycin-resistant Enterococci.","authors":"Vinay Sharma, Vengadesan Krishnan","doi":"10.1111/febs.70173","DOIUrl":"https://doi.org/10.1111/febs.70173","url":null,"abstract":"Enterococcus faecalis is an opportunistic pathogen that causes various clinically significant infections, including infective endocarditis and catheter-associated urinary tract infections. E. faecalis assembles hair-like appendages termed endocarditis and biofilm-associated pili (Ebp), crucial for adherence, colonization, biofilm formation, and virulence. The Ebp pilus comprises three pilin subunits (EbpA, EbpB, and EbpC) encoded by the ebpABC pilus operon. EbpC forms the Ebp pilus backbone decorated with EbpA and EbpB at the tip and base for adhesion and anchoring, respectively. Experimental structures are not yet available for any of the Ebp pilins. Herein, we report the crystal structures of EbpC, EbpB, and their homologs from E. faecium. The structures of EbpC and EbpB reveal four and three linearly arranged immunoglobulin-like domains, respectively. The basal pilin EbpB structure fully mimics the features of backbone pilins with a typical pilin motif and CnaB-CnaA-CnaB fold, each with an intact isopeptide bond. The rigid C-terminal fragment of the backbone pilin EbpC, containing three domains, exhibits a CnaB-CnaA-CnaB fold, each with an intradomain isopeptide bond. The flexible N-terminal domain with the CnaB fold in EbpC lacks an isopeptide bond but appears to form in a full-length structure that shows a 'beads on a string' architecture, previously unobserved for four-domain backbone pilins. Structural analysis helped us to identify residues of internal isopeptide bonds and pilin motifs harboring lysine residues responsible for intermolecular covalent links during sortase-mediated pilus assembly and propose a structural model for the Ebp pilus. This knowledge may be useful for developing structure-based approaches targeting pilins and pili in enterococcal infections.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Group A Streptococcus interacts with glycosaminoglycans via M proteins to modulate bacterial adherence in vitro. A群链球菌通过M蛋白与糖胺聚糖相互作用，调节体外细菌粘附。

The FEBS journal Pub Date : 2025-07-03 DOI: 10.1111/febs.70167

Tahnee B-D McEwan, David M P De Oliveira, Emily K Stares, Lauren E Hartley-Tassell, Christopher J Day, Mark J Walker, Michael P Jennings, Ronald Sluyter, Martina L Sanderson-Smith

{"title":"Group A Streptococcus interacts with glycosaminoglycans via M proteins to modulate bacterial adherence in vitro.","authors":"Tahnee B-D McEwan, David M P De Oliveira, Emily K Stares, Lauren E Hartley-Tassell, Christopher J Day, Mark J Walker, Michael P Jennings, Ronald Sluyter, Martina L Sanderson-Smith","doi":"10.1111/febs.70167","DOIUrl":"https://doi.org/10.1111/febs.70167","url":null,"abstract":"Glycosaminoglycans (GAGs) are enriched in the cutaneous extracellular matrix and have important roles in bacterial colonisation. Group A Streptococcus (GAS) can be categorised by emm patterning and M-family protein expression. M proteins of GAS are major adhesins with lectin-binding properties. This study aimed to provide a comprehensive specificity and affinity profile of phylogenetically diverse M proteins to a range of sulfated host GAGs and to investigate the physiological relevance of these interactions. Chondroitin sulfate preferentially associated with M proteins of A-C pattern strains, with binding localised to the central variable region of M1 protein. Dermatan sulfate was shown to associate with M proteins of all pattern type strains, with recognition involving multiple sites on M proteins. Heparin and heparan sulfate exclusively interacted with M proteins of A-C and D pattern strains. Multiple sites of M proteins were involved in heparin recognition, as indicated by surface plasmon resonance and site-directed mutagenesis of the heparin-binding XBXBX motif in the hypervariable-central region of M53 protein. In contrast, binding of heparan sulfate was localised to the non-repeat region between the B2 repeat and C1 repeat of M53 proteins. 5448 (M1-expressing GAS, A-C pattern) was shown to bind chondroitin sulfate, dermatan sulfate and heparin in an M protein-dependent manner. Furthermore, recruitment of chondroitin sulfate or dermatan sulfate by M1 proteins, but not heparin, was shown to increase GAS adherence to human HaCaT keratinocytes. This study increases our understanding of the molecular mechanisms underlying GAS adhesion, with key implications for bacterial colonisation and persistence of infection.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of N-linked glycans on the dual short fibulin/LTBP-4 axes regulating elastogenesis. n -链聚糖对调节弹性发生的双短纤维蛋白/LTBP-4轴的影响。

The FEBS journal Pub Date : 2025-07-03 DOI: 10.1111/febs.70171

Valentin Nelea, Heena Kumra, Chae Syng Lee, Daniel Williamson, Hana Hakami, Rong-Mo Zhang, Neha E H Dinesh, Robert Haltiwanger, Dieter P Reinhardt

{"title":"Impact of N-linked glycans on the dual short fibulin/LTBP-4 axes regulating elastogenesis.","authors":"Valentin Nelea, Heena Kumra, Chae Syng Lee, Daniel Williamson, Hana Hakami, Rong-Mo Zhang, Neha E H Dinesh, Robert Haltiwanger, Dieter P Reinhardt","doi":"10.1111/febs.70171","DOIUrl":"https://doi.org/10.1111/febs.70171","url":null,"abstract":"Elastic fibers are key extracellular components, providing elasticity to blood vessels, lungs, skin, and bladder. Elastic fiber formation requires the accessory proteins fibulin-4, fibulin-5, and the long and short isoforms of the latent TGFβ binding protein-4 (LTBP-4L/S). We established two molecular axes, LTBP-4L/fibulin-4 and LTBP-4S/fibulin-5, defined similar and distinct functions, and determined the role of N-linked glycans in this context. Glycoproteomic analysis identified the specific N-linked glycans in these proteins. Biophysical analyses revealed that the N-linked glycans of LTBP-4L, but not fibulin-4, were critical for fibulin-4-mediated conformational extension of LTBP-4L, impacting its function and assembly. Biochemical and recombinant removal of N-linked glycans from fibulin-4 enhanced its interaction with tropoelastin and elastic fiber formation, indicating an inhibitory role for these N-glycans. Fibulin-5 strongly interacted with and robustly induced a conformational extension of LTBP-4S, leading to enhanced binding to fibronectin, increased LTBP-4S deposition, and doubling of elastic fiber formation. Loss of N-linked glycans from fibulin-5, but not LTBP-4S, reduced their interaction by about 10-fold and abolished the ability of fibulin-5 to extend LTBP-4S conformationally. The presence of fibulin-5-extended LTBP-4S did not trigger tropoelastin aggregation in an in vitro assembly assay but boosted elastic fiber-like assembly massively when fibulin-4 and LTBP-4L were additionally present, suggesting synergistic effects. N-linked glycans in fibulin-5 were essential in this process. The study uncovers novel mechanisms that regulate elastic fiber formation, including overlapping and distinct roles of the LTBP-4L/fibulin-4 and the LTBP-4S/fibulin-5 axes and the importance of N-linked glycans of each of these proteins.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein kinase A: a quirky prototype. 蛋白激酶A：一个古怪的原型。

The FEBS journal Pub Date : 2025-07-02 DOI: 10.1111/febs.70176

Matthew G Gold

引用次数: 0

Human FASTK preferentially binds single-stranded and G-rich RNA. 人类FASTK优先结合单链和富含g的RNA。

The FEBS journal Pub Date : 2025-07-01 DOI: 10.1111/febs.70155

Daria M Dawidziak, Dawid A Dzadz, Mikołaj I Kuska, Madhuri Kanavalli, Maria M Klimecka, Matthew Merski, Katarzyna J Bandyra, Maria W Górna

{"title":"Human FASTK preferentially binds single-stranded and G-rich RNA.","authors":"Daria M Dawidziak, Dawid A Dzadz, Mikołaj I Kuska, Madhuri Kanavalli, Maria M Klimecka, Matthew Merski, Katarzyna J Bandyra, Maria W Górna","doi":"10.1111/febs.70155","DOIUrl":"https://doi.org/10.1111/febs.70155","url":null,"abstract":"Fas-activated serine/threonine kinase (FASTK) is the founding member of the FASTKD protein family, which was shown to regulate the fate of mRNA molecules on multiple levels. The mitochondrial variant of FASTK co-localizes with mitochondrial RNA granules and regulates the degradation of mitochondrial mRNAs, whereas the cytoplasmic and nuclear forms of FASTK are involved in the regulation of alternative splicing, cytoplasmic RNA granule formation, and mRNA translation. Despite these multiple roles of FASTK in mRNA biology, the exact rules of RNA recognition by this protein remained undetermined. Here, we demonstrate direct RNA binding by purified human FASTK and show its preference for single-stranded G-rich oligonucleotides, including those with a tendency to form RNA G-quadruplexes. Addition of FASTK alone was sufficient to achieve protection of mitochondrial mRNAs from degradation by the degradosome. Structural characterization by SAXS (Small-Angle X-ray Scattering) showed that FASTK in solution is a monomer with an extended conformation. Point mutagenesis studies supported the structural predictions of an exposed RNA-binding interface in the central helical region, preceded by a smaller, flexibly attached helical N-terminal domain. We provide the first such extensive in vitro characterization of the RNA binding properties for a representative of the FASTKD protein family and suggest how these intrinsic properties may underlie FASTK function in mRNA metabolism.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blood group O expression in normal tissues and tumors. O型血在正常组织及肿瘤中的表达。

The FEBS journal Pub Date : 2025-06-30 DOI: 10.1111/febs.70172

Ea Kristine Clarisse Tulin, Lukas Muerner, Tanya R McKitrick, Catherine A Tilton, Lauren E Pepi, Tianwei Jia, Maxence Noel, Leon Y Zheng, Sean R Stowell, Stephan von Gunten, Jamie Heimburg-Molinaro, Richard D Cummings

{"title":"Blood group O expression in normal tissues and tumors.","authors":"Ea Kristine Clarisse Tulin, Lukas Muerner, Tanya R McKitrick, Catherine A Tilton, Lauren E Pepi, Tianwei Jia, Maxence Noel, Leon Y Zheng, Sean R Stowell, Stephan von Gunten, Jamie Heimburg-Molinaro, Richard D Cummings","doi":"10.1111/febs.70172","DOIUrl":"10.1111/febs.70172","url":null,"abstract":"The H antigen (O blood group), the precursor to A and B blood groups, is expressed on human erythrocytes and other cells (e.g., endothelial cells). Remarkably, the specific expression of the H antigens is uncertain due to the lack of specific reagents for its detection. Here, we describe two monoclonal antibodies (mAbs), Tn4-31L and OmcFL3-02, generated by immunizing sea lampreys with human cells. Both mAbs are highly specific in comparison with the lectin Ulex europaeus agglutinin-I (UEA-I). We identified expression of H antigens in mammalian glycoproteins, human cells, and normal and malignant human tissues, discovering that different types of human carcinomas exhibit unexpected H antigen expression. Interestingly, H antigen detection in many cases was distinctly elevated by enzymatic desialylation, as well as being elevated in cells engineered to lack sialic acid. These highly specific mAbs will be valuable reagents in blood testing and for exploring the expression and function of H antigens.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crystal structure and biophysical characterisation of the enterococcal foldase PpiC, a cross-opsonic antigen against gram-positive nosocomial pathogens. 肠球菌折叠酶PpiC的晶体结构和生物物理特性，PpiC是一种抗革兰氏阳性医院病原体的交叉抗原。

The FEBS journal Pub Date : 2025-06-30 DOI: 10.1111/febs.70160

Valeria Napolitano, Eliza Kramarska, Ornella Ghilardi, Felipe Romero-Saavedra, Pompea Del Vecchio, Flavia Squeglia, Johannes Huebner, Rita Berisio

{"title":"Crystal structure and biophysical characterisation of the enterococcal foldase PpiC, a cross-opsonic antigen against gram-positive nosocomial pathogens.","authors":"Valeria Napolitano, Eliza Kramarska, Ornella Ghilardi, Felipe Romero-Saavedra, Pompea Del Vecchio, Flavia Squeglia, Johannes Huebner, Rita Berisio","doi":"10.1111/febs.70160","DOIUrl":"https://doi.org/10.1111/febs.70160","url":null,"abstract":"Enterococcus faecium have high rates of antibiotic resistances, with vancomycin-resistant E. faecium acknowledged as the most important in the clinical setting and declared by WHO to be a threat to humankind, for which rapid actions are needed. PpiC is a membrane-bound lipoprotein of E. faecium endowed with both a peptidyl-prolyl isomerase and a foldase activity, and plays a key role in assisting the folding of many secreted enterococcal proteins. It is located at the membrane-wall interface, therefore easily accessible to inhibitors and to the immune system and an ideal target for drug and vaccine development. Despite their potential, enterococcal peptidyl-prolyl isomerases have been understudied. We previously identified PpiC as an important cross-protective vaccine antigen. To gain a better understanding of the PpiC biological role in E. faecium survival, we determined the crystal structure of PpiC and investigated its biophysical properties. Consistent with PpiC's folding activity, the biological assembly of PpiC is a bowl-shaped structure containing two parvulin-type peptidyl-prolyl cis/trans isomerase domains. We also dissected the role of N- and C-terminal regions of the molecule in its dimerisation, an event which is predicted to play an important role in the folding of client proteins. Our data point to a functional cross-talk between the foldase and peptidyl-prolyl isomerase activities of PpiC, through the protein-swapping involved in dimerisation. Also, our work provides key structural data for the design of antimicrobials and cross-protective vaccine antigens against nosocomial infections.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasmodium falciparum acetyltransferase GCN5 acts as a dual regulator of essential glycolytic enzyme phosphoglycerate mutase. 恶性疟原虫乙酰转移酶GCN5作为必需糖酵解酶磷酸甘油酸变异酶的双重调节因子。

The FEBS journal Pub Date : 2025-06-26 DOI: 10.1111/febs.70164

Ankita Tehlan, Poonam Nagar, Reena Prajapati, Krishanu Bhowmick, Amarjeet Kumar, Inderjeet Kaur, Naidu Subbarao, Suman Kumar Dhar

{"title":"Plasmodium falciparum acetyltransferase GCN5 acts as a dual regulator of essential glycolytic enzyme phosphoglycerate mutase.","authors":"Ankita Tehlan, Poonam Nagar, Reena Prajapati, Krishanu Bhowmick, Amarjeet Kumar, Inderjeet Kaur, Naidu Subbarao, Suman Kumar Dhar","doi":"10.1111/febs.70164","DOIUrl":"https://doi.org/10.1111/febs.70164","url":null,"abstract":"Lysine acetylation is emerging as a key player in cellular regulation across species by controlling the fate of metabolic proteins as well as modulating gene expression via histone modification. Phosphoglycerate mutase, a conserved enzyme of the sole energy-yielding pathway of glycolysis in the human malaria parasite Plasmodium falciparum, is indispensable for its growth. Here, we demonstrate that P. falciparum phosphoglycerate mutase PfPGM1 (phosphoglycerate mutase) is regulated via lysine acetylation. In mammalian cells, acetylation of phosphoglycerate mutase modulates its catalytic activity, although the acetyl transferase enzyme remains elusive. However, the parasites exhibit a unique way of regulating the fate of PfPGM1 via acetylation that modulates its stability, thus providing an increased protein pool for the rapid growth and proliferation of the parasites. We show that K100, a critical residue for PfPGM1 catalytic activity, is acetylated by the essential histone acetyltransferase PfGCN5. Downregulation of PfGCN5 through a knockdown approach in the parasites along with cycloheximide treatment indeed leads to a reduction of PfPGM1 protein. Additionally, PfGCN5 occupies the promoter of PfPGM1 in a stage-specific manner, and downregulation of PfGCN5 protein leads to a reduced transcript level of PfPGM1. Collectively, our data highlight a dual regulation of PfPGM1 by PfGCN5 through acetylation of the protein as well as regulation of the transcription of the gene. Such dual control is not only rare but showcases the importance of the above two proteins and their potential as excellent targets against malaria.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Studies of the membrane-bound flavocytochrome MsrQ flavin mononucleotide (FMN)-binding site reveal an unexpected ubiquinone cofactor. 膜结合黄细胞色素MsrQ黄素单核苷酸（FMN）结合位点的研究揭示了一个意想不到的泛素辅助因子。

The FEBS journal Pub Date : 2025-06-26 DOI: 10.1111/febs.70162

Philippe Carpentier, Fabien Pierrel, Nicolas Duraffourg, Bruno Guigliarelli, Mahmoud Hajj Chehade, Laura Flandrin, Christian Basset, Christelle Caux, Stéphane Torelli, Vincent Nivière

{"title":"Studies of the membrane-bound flavocytochrome MsrQ flavin mononucleotide (FMN)-binding site reveal an unexpected ubiquinone cofactor.","authors":"Philippe Carpentier, Fabien Pierrel, Nicolas Duraffourg, Bruno Guigliarelli, Mahmoud Hajj Chehade, Laura Flandrin, Christian Basset, Christelle Caux, Stéphane Torelli, Vincent Nivière","doi":"10.1111/febs.70162","DOIUrl":"https://doi.org/10.1111/febs.70162","url":null,"abstract":"The methionine sulfoxide reductase PQ system (MsrPQ) is a newly identified type of bacterial methionine sulfoxide reductase (Msr) involved in the repair of periplasmic methionine residues that have been oxidized by hypochlorous acid. MsrP, which carries out the Msr activity, is a molybdoenzyme located in the periplasm, whereas MsrQ, an integral membrane-bound flavohemoprotein, specifically transfers electrons to MsrP to drive catalysis. MsrQ belongs to an important superfamily of heme-containing membrane-bound proteins, which includes the eukaryotic NADPH oxidases (NOX) and six-transmembrane epithelial antigen of the prostate (STEAP) ferric reductases. Like STEAP, and in addition to a b-type heme, MsrQ contains a flavin cofactor [flavin mononucleotide (FMN)], which mediates electron transfer from a cytosolic NADH oxidoreductase to the heme, and subsequently to MsrP. In this study, we characterized the FMN-binding site of MsrQ using an AlphaFold model, identifying R77 and R78 residues as potentially critical for FMN stabilization. The R77A and R78A mutations result in the complete loss of the FMN cofactor, showing that both residues are essential for FMN binding. Surprisingly, electron paramagnetic resonance (EPR) spectroscopy and biochemical analysis of the mutants revealed the presence of a ubiquinone (UQ) cofactor associated with MsrQ, independently of the binding of FMN. The mid-point redox potentials of the MsrQ heme and FMN cofactors, measured through redox titration and cyclic voltammetry experiments, contradict the previous assumption that UQ serves as the electron donor for MsrQ. Instead, our data suggest that UQ may function as an electron acceptor for the reduced form of MsrQ. We propose that UQ bound to MsrQ could act as a protective mechanism when MsrP substrate is limiting.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cryo-EM structural analyses reveal a unique role for elongation factor G2 (EF-G2) in Mycobacteria. 低温电镜结构分析揭示了延伸因子G2 （EF-G2）在分枝杆菌中的独特作用。

The FEBS journal Pub Date : 2025-06-26 DOI: 10.1111/febs.70161

Priya Baid, Jayati Sengupta

{"title":"Cryo-EM structural analyses reveal a unique role for elongation factor G2 (EF-G2) in Mycobacteria.","authors":"Priya Baid, Jayati Sengupta","doi":"10.1111/febs.70161","DOIUrl":"https://doi.org/10.1111/febs.70161","url":null,"abstract":"The gene-encoding translation elongation factor G (EF-G) has undergone gene duplication across various bacterial species including Mycobacteria, and in mammalian mitochondria, leading to the emergence of the paralogue elongation factor G2 (EF-G2). Our study reveals that mycobacterial EF-G2, unlike EF-G1, neither participates in ribosome-recycling nor significantly contributes to overall translation, suggesting that it plays an alternative role in Mycobacteria. Remarkably, our investigation found a significant overexpression of mycobacterial EF-G2 during the stationary growth phase. Moreover, EF-G2 lacks ribosome-dependent GTPase activity, an observation consistent with previous reports. Cryo-EM analysis of the M. smegmatis 70S ribosome purified from the nutrient-starved (stationary) phase and complexed with EF-G2 unveiled the structural basis for its inability to hydrolyse GTP in a ribosome-dependent manner. Furthermore, we report an unprecedented binding mode of two EF-G2 copies on the 50S ribosomal subunit that impedes subunit association, thereby preventing the formation of active 70S ribosomes. Thus, instead of performing canonical functions, mycobacterial EF-G2 acts as a translation repressor during nutrient starvation. Altogether, our findings shed light on the multifaceted mechanisms by which EF-G2 modulates protein synthesis under nutrient-limited conditions, providing insights into adaptive strategies employed by Mycobacteria to survive in hostile environments.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0