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Archaeal NusA2 is the ancestor of ribosomal protein eS7 in eukaryotes 古生物 NusA2 是真核生物核糖体蛋白 eS7 的祖先
IF 5.7 2区 生物学
Structure Pub Date : 2024-11-05 DOI: 10.1016/j.str.2024.10.019
Duy Khanh Phung, Simona Pilotto, Dorota Matelska, Fabian Blombach, Nikos Pinotsis, Ladislav Hovan, Francesco Luigi Gervasio, Finn Werner
{"title":"Archaeal NusA2 is the ancestor of ribosomal protein eS7 in eukaryotes","authors":"Duy Khanh Phung, Simona Pilotto, Dorota Matelska, Fabian Blombach, Nikos Pinotsis, Ladislav Hovan, Francesco Luigi Gervasio, Finn Werner","doi":"10.1016/j.str.2024.10.019","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.019","url":null,"abstract":"N-utilization substance A (NusA) is a regulatory factor with pleiotropic functions in gene expression in bacteria. Archaea encode two conserved small proteins, NusA1 and NusA2, with domains orthologous to the two RNA binding K Homology (KH) domains of NusA. Here, we report the crystal structures of NusA2 from <em>Sulfolobus acidocaldarius</em> and <em>Saccharolobus solfataricus</em> obtained at 3.1 Å and 1.68 Å, respectively. NusA2 comprises an N-terminal zinc finger followed by two KH-like domains lacking the GXXG signature. Despite the loss of the GXXG motif, NusA2 binds single-stranded RNA. Mutations in the zinc finger domain compromise the structural integrity of NusA2 at high temperatures and molecular dynamics simulations indicate that zinc binding provides an energy barrier preventing the domain from reaching unfolded states. A structure-guided phylogenetic analysis of the KH-like domains supports the notion that the NusA2 clade is ancestral to the ribosomal protein eS7 in eukaryotes, implying a potential role of NusA2 in translation.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"10 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Two cooperative lipid binding sites within the pleckstrin homology domain are necessary for AKT binding and stabilization to the plasma membrane pleckstrin同源结构域中的两个合作脂质结合位点是AKT与质膜结合和稳定的必要条件
IF 5.7 2区 生物学
Structure Pub Date : 2024-11-05 DOI: 10.1016/j.str.2024.10.020
Chrysa Soteriou, Mengfan Xu, Simon D. Connell, Arwen I.I. Tyler, Antreas C. Kalli, James L. Thorne
{"title":"Two cooperative lipid binding sites within the pleckstrin homology domain are necessary for AKT binding and stabilization to the plasma membrane","authors":"Chrysa Soteriou, Mengfan Xu, Simon D. Connell, Arwen I.I. Tyler, Antreas C. Kalli, James L. Thorne","doi":"10.1016/j.str.2024.10.020","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.020","url":null,"abstract":"Almost four decades after the identification of the AKT protein and understanding of its role in cancer, barriers remain in the translation of AKT inhibitors for clinical applications. Here, we provide new molecular insight into the first step of AKT activation where AKT binds to the plasma membrane and its orientation is stabilized in a bilayer with lateral heterogeneity (L<sub>o</sub>-L<sub>d</sub> phase coexistence). We have applied molecular dynamic simulations and molecular and cell biology approaches, and demonstrate that AKT recruitment to the membrane requires a second binding site in the AKT pleckstrin homology (PH) domain that acts cooperatively with the known canonical binding site. Given the precision with which we have identified the protein-lipid interactions, the study offers new directions for AKT-targeted therapy and for testing small molecules to target these specific amino acid-PIP molecular bonds.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"129 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Crystal structure of the alternative complex III from the phototrophic bacterium Chloroflexus aurantiacus 光营养细菌 Chloroflexus aurantiacus 的替代复合体 III 的晶体结构
IF 5.7 2区 生物学
Structure Pub Date : 2024-11-04 DOI: 10.1016/j.str.2024.10.014
Wenping Wu, Han Fang, Huimin He, Jingyi Wu, Zijun Gong, Chunyang Li, Xinkai Pei, Xiaoling Xu
{"title":"Crystal structure of the alternative complex III from the phototrophic bacterium Chloroflexus aurantiacus","authors":"Wenping Wu, Han Fang, Huimin He, Jingyi Wu, Zijun Gong, Chunyang Li, Xinkai Pei, Xiaoling Xu","doi":"10.1016/j.str.2024.10.014","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.014","url":null,"abstract":"Alternative complex III (ACIII) is a multi-subunit quinol:electron acceptor oxidoreductase that couples quinol oxidation with transmembrane proton translocation in bacterial respiratory and photosynthetic electron transport chains. Four ACIII cryoelectron microscopy (cryo-EM) structures are known. However, the effects of cryo-EM versus X-ray crystallography structure determination on ACIII structure are unclear. Here, we report a 3.25 Å crystal structure of photosynthetic ACIII from <em>Chloroflexus aurantiacus</em> (<em>Ca</em>ACIIIp), revealing eight subunits (ActA–G and I) with four iron-sulfur clusters and six <em>c</em>-type hemes, a menaquinol-binding site, and two proton translocation passages. Structural comparisons with the previously reported cryo-EM structures reveal slight local conformational changes in the solvent-exposed regions of ActB, ActD, ActG, and the transmembrane (TM) helix of subunit I. The regions conferring structural flexibility possess low sequence conservation across species. However, the core functional modules containing the menaquinol-binding pocket, redox centers, and proton translocation passages remain unchanged, preserving the enzyme’s activity.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"73 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LEDGF interacts with the NID domain of MeCP2 and modulates MeCP2 condensates LEDGF与MeCP2的NID结构域相互作用并调节MeCP2的凝结
IF 5.7 2区 生物学
Structure Pub Date : 2024-11-04 DOI: 10.1016/j.str.2024.10.016
Saskia Lesire, Rodrigo Lata, Yannick Hoogvliets, Kune Herrebosch, Paulien Van De Velde, Anouk Speleers, Frauke Christ, Siska Van Belle, Zeger Debyser
{"title":"LEDGF interacts with the NID domain of MeCP2 and modulates MeCP2 condensates","authors":"Saskia Lesire, Rodrigo Lata, Yannick Hoogvliets, Kune Herrebosch, Paulien Van De Velde, Anouk Speleers, Frauke Christ, Siska Van Belle, Zeger Debyser","doi":"10.1016/j.str.2024.10.016","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.016","url":null,"abstract":"Methyl-CpG-binding protein 2 (MeCP2) is a ubiquitously expressed nuclear protein involved in transcriptional regulation and chromatin remodeling. MeCP2 exists in two isoforms, MeCP2 E1 and E2, which share the same functional domains. Loss-of-function mutations in the MeCP2 gene are the main cause of Rett syndrome (RTT). Previous studies identified a complex formation between MeCP2 and lens epithelium derived growth factor (LEDGF), a transcriptional regulator that exists in two isoforms, LEDGF/p75 and LEDGF/p52. Here, we characterized the molecular and functional interaction between MeCP2 and LEDGF. The NCoR interaction domain (NID) domain in MeCP2 is essential for the direct binding to the PWWP-CR1 region of LEDGF. Introduction of R306C, an RTT mutation in the NID of MeCP2, reduced the interaction with LEDGF. Our data reveal mutual inhibition of MeCP2 and LEDGF multimerization due to overlapping binding sites. Aligning with this observation, LEDGF depletion resulted in larger MeCP2 and DNA foci in NIH3T3 cells, suggesting a role for the MeCP2-LEDGF complex in chromatin organization.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"87 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structure-function analyses of human TRPV6 ancestral and derived haplotypes 人类 TRPV6 祖先和衍生单倍型的结构功能分析
IF 5.7 2区 生物学
Structure Pub Date : 2024-11-04 DOI: 10.1016/j.str.2024.10.018
Arthur Neuberger, Alexey Shalygin, Yury A. Trofimov, Irina I. Veretenenko, Kirill D. Nadezhdin, Nikolay A. Krylov, Thomas Gudermann, Roman G. Efremov, Vladimir Chubanov, Alexander I. Sobolevsky
{"title":"Structure-function analyses of human TRPV6 ancestral and derived haplotypes","authors":"Arthur Neuberger, Alexey Shalygin, Yury A. Trofimov, Irina I. Veretenenko, Kirill D. Nadezhdin, Nikolay A. Krylov, Thomas Gudermann, Roman G. Efremov, Vladimir Chubanov, Alexander I. Sobolevsky","doi":"10.1016/j.str.2024.10.018","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.018","url":null,"abstract":"TRPV6 is a Ca<sup>2+</sup> selective channel that mediates calcium uptake in the gut and contributes to the development and progression of human cancers. TRPV6 is represented by the ancestral and derived haplotypes that differ by three non-synonymous polymorphisms, located in the N-terminal ankyrin repeat domain (C157R), S1–S2 extracellular loop (M378V), and C-terminus (M681T). The ancestral and derived haplotypes were proposed to serve as genomic factors causing a different outcome for cancer patients of African ancestry. We solved cryoelectron microscopy (cryo-EM) structures of ancestral and derived TRPV6 in the open and calmodulin (CaM)-bound inactivated states. Neither state shows substantial structural differences caused by the non-synonymous polymorphisms. Functional properties assessed by electrophysiological recordings and Ca<sup>2+</sup> uptake measurements, and water and ion permeation evaluated by molecular modeling also appear similar between the haplotypes. Therefore, ancestral and derived TRPV6 have similar structure and function, implying that other factors are responsible for the differences in susceptibility to cancer.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"67 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-resolution cryo-EM analysis of a Streptococcus pyogenes M-protein/human plasminogen complex 化脓性链球菌 M 蛋白/人纤溶酶原复合物的高分辨率冷冻电镜分析
IF 5.7 2区 生物学
Structure Pub Date : 2024-11-04 DOI: 10.1016/j.str.2024.10.003
Bradley M. Readnour, Sheiny Tjia-Fleck, Nathan R. McCann, Yetunde A. Ayinuola, Francis J. Castellino
{"title":"High-resolution cryo-EM analysis of a Streptococcus pyogenes M-protein/human plasminogen complex","authors":"Bradley M. Readnour, Sheiny Tjia-Fleck, Nathan R. McCann, Yetunde A. Ayinuola, Francis J. Castellino","doi":"10.1016/j.str.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.003","url":null,"abstract":"The importance of human plasminogen (hPg)/plasmin (hPm)/cell receptor complexes in invasiveness of cells has been amply established. The objective of this investigation was to determine a high-resolution structure of a major Group A <em>Streptococcus</em> (GAS) bacterial receptor (PAM) for hPg/hPm when bound on a cell surface to its major ligand, hPg. As a model cell surface with endogenous PAM, we employed engineered PAM-expressing lentivirus (LV) particles. We show that the ectodomain of a PAM-type M-Protein (M-Prt), in complex with hPg, is folded through distinct intra- and inter-domain interactions to a more compact form on the cell surface, thus establishing a new paradigm for membrane-bound M-Prt/ligand structures. These studies provide a framework for addressing the need for treatments of GAS disease by providing a molecular platform to solve structures of virulence-determining membrane proteins.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"9 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tau seeds catalyze fibril-type structures from GFP tau biosensor cells Tau 种子催化 GFP tau 生物传感器细胞形成纤维状结构
IF 5.7 2区 生物学
Structure Pub Date : 2024-11-01 DOI: 10.1016/j.str.2024.10.013
Jinliang Wang, Christopher K. Williams, Michael A. DeTure, Shino D. Magaki, Dennis W. Dickson, Harry V. Vinters, Paul M. Seidler
{"title":"Tau seeds catalyze fibril-type structures from GFP tau biosensor cells","authors":"Jinliang Wang, Christopher K. Williams, Michael A. DeTure, Shino D. Magaki, Dennis W. Dickson, Harry V. Vinters, Paul M. Seidler","doi":"10.1016/j.str.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.013","url":null,"abstract":"Fibril-type aggregates of tau occur in Alzheimer’s disease (AD) and dozens of tauopathies. Fibrils catalyze aggregation by prion-like seeding, which in part underlies disease progression. Seeding by recombinant and brain-derived tau fibrils is measured using biosensor cells that express aggregation-prone tau mutants fused with fluorescent reporter proteins. Seeding results in a punctated phenotype that is well established, but evidence that fluorescent tau fusion proteins from biosensor cells assemble into fibril-type structures is lacking. We investigated the effects of seeding on fibril formation by biosensor cells. Fluorescent punctated cell phenotypes that were catalyzed persisted with varying stabilities. Seeded cells bearing punctated phenotypes yielded sarkosyl-insoluble fibrils, although non-seeded cells did not. ImmunoEM of cell-purified fibrils shows that GFP localizes to the proteolytically sensitive fuzzy coat of tau fibrils. The presented data offer compelling evidence that fluorescent puncta are fibril-type aggregates of tau that result from prion-like seeding.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"67 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GeoNet enables the accurate prediction of protein-ligand binding sites through interpretable geometric deep learning 通过可解释的几何深度学习,GeoNet 可准确预测蛋白质配体结合位点
IF 5.7 2区 生物学
Structure Pub Date : 2024-11-01 DOI: 10.1016/j.str.2024.10.011
Jiyun Han, Shizhuo Zhang, Mingming Guan, Qiuyu Li, Xin Gao, Juntao Liu
{"title":"GeoNet enables the accurate prediction of protein-ligand binding sites through interpretable geometric deep learning","authors":"Jiyun Han, Shizhuo Zhang, Mingming Guan, Qiuyu Li, Xin Gao, Juntao Liu","doi":"10.1016/j.str.2024.10.011","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.011","url":null,"abstract":"The identification of protein binding residues is essential for understanding their functions <em>in vivo</em>. However, it remains a computational challenge to accurately identify binding sites due to the lack of known residue binding patterns. Local residue spatial distribution and its interactive biophysical environment both determine binding patterns. Previous methods could not capture both information simultaneously, resulting in unsatisfactory performance. Here, we present GeoNet, an interpretable geometric deep learning model for predicting DNA, RNA, and protein binding sites by learning the latent residue binding patterns. GeoNet achieves this by introducing a coordinate-free geometric representation to characterize local residue distributions and generating an eigenspace to depict local interactive biophysical environments. Evaluation shows that GeoNet is superior compared to other leading predictors and it shows a strong interpretability of learned representations. We present three test cases, where interaction interfaces were successfully identified with GeoNet.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"136 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural and functional studies of the EGF20-27 region reveal new features of the human Notch receptor important for optimal activation 对 EGF20-27 区域的结构和功能研究揭示了人类 Notch 受体对于最佳激活的新特征
IF 5.7 2区 生物学
Structure Pub Date : 2024-11-01 DOI: 10.1016/j.str.2024.10.012
Zhihan Bo, Thomas Rowntree, Steven Johnson, Hilman Nurmahdi, Richard J. Suckling, Johan Hill, Boguslawa Korona, Philip C. Weisshuhn, Devon Sheppard, Yao Meng, Shaoyan Liang, Edward D. Lowe, Susan M. Lea, Christina Redfield, Penny A. Handford
{"title":"Structural and functional studies of the EGF20-27 region reveal new features of the human Notch receptor important for optimal activation","authors":"Zhihan Bo, Thomas Rowntree, Steven Johnson, Hilman Nurmahdi, Richard J. Suckling, Johan Hill, Boguslawa Korona, Philip C. Weisshuhn, Devon Sheppard, Yao Meng, Shaoyan Liang, Edward D. Lowe, Susan M. Lea, Christina Redfield, Penny A. Handford","doi":"10.1016/j.str.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.012","url":null,"abstract":"The Notch receptor is activated by the Delta/Serrate/Lag-2 (DSL) family of ligands. The organization of the extracellular signaling complex is unknown, although structures of Notch/ligand complexes comprising the ligand-binding region (LBR), and negative regulatory region (NRR) region, have been solved. Here, we investigate the human Notch-1 epidermal growth factor-like (EGF) 20-27 region, located between the LBR and NRR, and incorporating the Abruptex (Ax) region, associated with distinctive <em>Drosophila</em> phenotypes. Our analyses, using crystallography, NMR and small angle X-ray scattering (SAXS), support a rigid, elongated organization for EGF20-27 with the EGF20-21 linkage showing Ca<sup>2+</sup>-dependent flexibility. In functional assays, Notch-1 variants containing Ax substitutions result in reduced ligand-dependent <em>trans</em>-activation. When <em>cis</em>-JAG1 was expressed, Notch activity differences between WT and Ca<sup>2+</sup>-binding Ax variants were less marked than seen in the <em>trans</em>-activation assays alone, consistent with disruption of <em>cis</em>-inhibition. These data indicate the importance of Ca<sup>2+</sup>-stabilized structure and suggest the balance of <em>cis</em>- and <em>trans</em>-interactions explains the effects of <em>Drosophila Ax</em> mutations.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"6 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
T6SS-associated Rhs toxin-encapsulating shells: Structural and bioinformatical insights into bacterial weaponry and self-protection 与 T6SS 相关的 Rhs 毒素包裹壳:从结构和生物信息学角度洞察细菌武器与自我保护
IF 5.7 2区 生物学
Structure Pub Date : 2024-10-30 DOI: 10.1016/j.str.2024.10.008
Claudia S. Kielkopf, Mikhail M. Shneider, Petr G. Leiman, Nicholas M.I. Taylor
{"title":"T6SS-associated Rhs toxin-encapsulating shells: Structural and bioinformatical insights into bacterial weaponry and self-protection","authors":"Claudia S. Kielkopf, Mikhail M. Shneider, Petr G. Leiman, Nicholas M.I. Taylor","doi":"10.1016/j.str.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.008","url":null,"abstract":"Bacteria use the type VI secretion system (T6SS) to secrete toxins into pro- and eukaryotic cells via machinery consisting of a contractile sheath and a rigid tube. Rearrangement hotspot (Rhs) proteins represent one of the most common T6SS effectors. The Rhs C-terminal toxin domain displays great functional diversity, while the Rhs core is characterized by YD repeats. We elucidate the Rhs core structures of PAAR- and VgrG-linked Rhs proteins from <em>Salmonella bongori</em> and <em>Advenella mimigardefordensis</em>, respectively. The Rhs core forms a large shell of β-sheets with a negatively charged interior and encloses a large volume. The <em>S. bongori</em> Rhs toxin does not lead to ordered density in the Rhs shell, suggesting the toxin is unfolded. Together with bioinformatics analysis showing that Rhs toxins predominantly act intracellularly, this suggests that the Rhs core functions two-fold, as a safety feature for the producer cell and as delivery mechanism for the toxin.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"15 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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