IF 5.7 2区生物学

Structure Pub Date : 2025-03-31 DOI: 10.1016/j.str.2025.03.006

Subin Kim, Ji Won Kim, Jun Gyou Park, Sang Soo Lee, Seung Hun Choi, Jie-Oh Lee, Mi Sun Jin

引用次数: 0

ATP binding controls the molecular function of bacterial MutS2 by mediating closure of the dimeric clamp structure

IF 5.7 2区生物学

Structure Pub Date : 2025-03-28 DOI: 10.1016/j.str.2025.03.003

Kenji Fukui, Takeshi Murakawa, Nobumasa Hino, Naoyuki Kondo, Takato Yano

引用次数: 0

Structural basis for the constitutive activity of the melanocortin receptor family

IF 5.7 2区生物学

Structure Pub Date : 2025-03-28 DOI: 10.1016/j.str.2025.03.004

Wenbo Feng, Qingtong Zhou, Chang Zheng, Dehua Yang, Ming-Wei Wang

引用次数: 0

A mesophilic Argonaute from Clostridium formicaceticum with efficient DNA cleavage activity guided by small DNA

IF 5.7 2区生物学

Structure Pub Date : 2025-03-28 DOI: 10.1016/j.str.2025.03.002

Jianrui Li, Meixia Yu, Zhijia Yang, Yueheng Zhou, Yunpeng Teng, Zijian Wang, Jian Chen, Jinsheng Lai, Beibei Xin

{"title":"A mesophilic Argonaute from Clostridium formicaceticum with efficient DNA cleavage activity guided by small DNA","authors":"Jianrui Li, Meixia Yu, Zhijia Yang, Yueheng Zhou, Yunpeng Teng, Zijian Wang, Jian Chen, Jinsheng Lai, Beibei Xin","doi":"10.1016/j.str.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.str.2025.03.002","url":null,"abstract":"We characterized a new Argonaute protein (pAgo), CfAgo, from the mesophilic bacterium Clostridium formicaceticum. CfAgo possesses DNA-guided DNA endonuclease activity and cleaves DNA targets at the canonical site. It is active from 28°C to 75°C and prefers DNA guides with a 5′-phosphate group and thymidine as the first nucleotide. Cleavage activity is reduced by single-nucleotide mismatches in the seed, central, and 3′-supplementary regions of guides, with stronger mismatch discrimination observed for 5′hydroxylated (5′OH) guides compared to 5′phosphorylated (5′P) guides. Moreover, structural analysis suggests that the MID domain of CfAgo is crucial for recognizing the 5′ guide and it influences the binding specificity. CfAgo catalyzes programmable cleavage of double-stranded DNA in AT-rich regions in the presence of Mn2+ and Mg2+ ions at appropriate salt concentrations. These properties could make CfAgo a promising tool for DNA manipulation such as nucleic acid detection and cleavage.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"15 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723814","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

Structurally diverse C-terminal accessory domains in type I ABC importers reveal distinct regulatory mechanisms

IF 5.7 2区生物学

Structure Pub Date : 2025-03-24 DOI: 10.1016/j.str.2025.02.014

Evan R. Buechel, Valentina S. Dimitrova, Alexandra Karagiaridi, Lydia G. Kenney, Heather W. Pinkett

引用次数: 0

A structural perspective on the temperature dependent activity of enzymes

IF 5.7 2区生物学

Structure Pub Date : 2025-03-21 DOI: 10.1016/j.str.2025.02.013

Matthew J. McLeod, Sarah A.E. Barwell, Todd Holyoak, Robert E. Thorne

{"title":"A structural perspective on the temperature dependent activity of enzymes","authors":"Matthew J. McLeod, Sarah A.E. Barwell, Todd Holyoak, Robert E. Thorne","doi":"10.1016/j.str.2025.02.013","DOIUrl":"https://doi.org/10.1016/j.str.2025.02.013","url":null,"abstract":"Enzyme activity varies with temperature. Unlike small-molecule catalysts, the structural ensembles of enzymes can change substantially with temperature, but it is unclear how this modulates temperature dependent activity. Here, multi-temperature X-ray crystallography was used to record structural changes from ˗20°C to 40°C for a mesophilic enzyme in complex with inhibitors mimicking substrate-, intermediate-, and product-bound states, representative of major complexes on the reaction coordinate. Inhibitors, substrates and active site loops increasingly populated catalytically competent conformations as temperature increased. These changes occurred even in temperature ranges where kinetic measurements showed roughly linear Arrhenius/Eyring behavior, where parameters characterizing the system are assumed to be temperature independent. Simple analysis shows that linear Arrhenius/Eyring behavior can still be observed when the underlying activation energy/enthalpy values vary with temperature. Our results indicate a critical role for temperature dependent atomic-resolution structural data in interpreting temperature dependent kinetic data from enzymatic systems.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666284","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

Cryo-EM structure of the human monocarboxylate transporter 10

IF 5.7 2区生物学

Structure Pub Date : 2025-03-19 DOI: 10.1016/j.str.2025.02.012

Viktoria Bågenholm, Karl Patric Nordlin, Andrea Pasquadibisceglie, Andrey Belinskiy, Caroline Marcher Holm, Hajira Ahmed Hotiana, Kamil Gotfryd, Lucie Delemotte, Hussam Hassan Nour-Eldin, Per Amstrup Pedersen, Pontus Gourdon

{"title":"Cryo-EM structure of the human monocarboxylate transporter 10","authors":"Viktoria Bågenholm, Karl Patric Nordlin, Andrea Pasquadibisceglie, Andrey Belinskiy, Caroline Marcher Holm, Hajira Ahmed Hotiana, Kamil Gotfryd, Lucie Delemotte, Hussam Hassan Nour-Eldin, Per Amstrup Pedersen, Pontus Gourdon","doi":"10.1016/j.str.2025.02.012","DOIUrl":"https://doi.org/10.1016/j.str.2025.02.012","url":null,"abstract":"The monocarboxylate transporter (MCT) membrane protein family has 14 human members that perform key cellular functions, such as regulating metabolism. MCT8 and MCT10 have unique cargo specificity, transporting thyroid hormone and, in the case of MCT10, aromatic amino acids. Dysfunctional MCT8 causes the severe Allan-Herndon-Dudley syndrome, yet the (patho)physiology and function of MCT8 and MCT10 are not clearly understood, especially at a structural level. We present the cryoelectron microscopy (cryo-EM) structure of MCT10, displaying the classical major facilitator superfamily fold, caught in an inward-open configuration. Together with cargo docking models, the outward-open MCT10 AlphaFold model and validating functional analysis, cargo specificity and transport principles are proposed. These findings significantly enhance our understanding of the structure and function of MCTs, information that also may be valuable for the development of novel treatments against MCT-related disorders to address global challenges such as diabetes, obesity, and cancer.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"61 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653798","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

Distinct binding modes drive the broad neutralization profile of two persistent influenza hemagglutinin stem-specific antibody lineages

IF 5.7 2区生物学

Structure Pub Date : 2025-03-19 DOI: 10.1016/j.str.2025.02.010

Grace E. Mantus, Gabriele Cerutti, Michael Chambers, Rebecca A. Gillespie, Geoffrey D. Shimberg, Abby Spangler, Jason Gorman, Tongqing Zhou, Chen-Hsiang Shen, Masaru Kanekiyo, Peter D. Kwong, Lawrence Shapiro, Sarah F. Andrews

{"title":"Distinct binding modes drive the broad neutralization profile of two persistent influenza hemagglutinin stem-specific antibody lineages","authors":"Grace E. Mantus, Gabriele Cerutti, Michael Chambers, Rebecca A. Gillespie, Geoffrey D. Shimberg, Abby Spangler, Jason Gorman, Tongqing Zhou, Chen-Hsiang Shen, Masaru Kanekiyo, Peter D. Kwong, Lawrence Shapiro, Sarah F. Andrews","doi":"10.1016/j.str.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.str.2025.02.010","url":null,"abstract":"Elicitation of antibodies to the influenza hemagglutinin stem is a critical part of universal influenza vaccine strategies. While numerous broadly reactive stem antibodies have been isolated, our understanding of how these antibodies mature within the human B cell repertoire is limited. Here, we isolated and tracked two stem-specific antibody lineages over a decade in a single participant that received multiple seasonal and pandemic influenza vaccinations. Despite similar binding and neutralization profiles, antibodies from these lineages utilized fundamentally different interactions to engage the central epitope on the influenza stem. Structural analysis of an unmutated common ancestor from one lineage identified critical residues that were the main drivers of increased affinity and breadth to group 1 influenza subtypes. These observations demonstrate the heterogeneous pathways by which stem-specific antibodies can mature within the human B cell repertoire.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"197 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653797","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

Molecular basis of Ad5-nCoV vaccine-induced immunogenicity

IF 5.7 2区生物学

Structure Pub Date : 2025-03-19 DOI: 10.1016/j.str.2025.02.009

Dongyang Dong, Yutong Song, Shipo Wu, Busen Wang, Cheng Peng, Weiping Zhang, Weizheng Kong, Zheyuan Zhang, Jingwen Song, Li-Hua Hou, Sai Li

{"title":"Molecular basis of Ad5-nCoV vaccine-induced immunogenicity","authors":"Dongyang Dong, Yutong Song, Shipo Wu, Busen Wang, Cheng Peng, Weiping Zhang, Weizheng Kong, Zheyuan Zhang, Jingwen Song, Li-Hua Hou, Sai Li","doi":"10.1016/j.str.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.str.2025.02.009","url":null,"abstract":"Ad5-nCoV (Convidecia) is listed for emergency use against COVID-19 by the World Health Organization (WHO) and has been globally administered to millions of people. It utilizes human adenovirus 5 (Ad5) replication-incompetent vector to deliver the spike (S) protein gene from various SARS-CoV-2 strains. Despite promising clinical data, the molecular mechanism underlying its high immunogenicity and adverse reactions remain incompletely understood. Here, we primarily applied cryo-electron tomography (cryo-ET), fluorescence microscopy and mass spectrometry to analyze the Ad5-nCoV_Wu and Ad5-nCoV_O vaccine-induced S antigens. These antigens encode the unmodified SARS-CoV-2 Wuhan-Hu-1 S gene and the stabilized Omicron S gene, respectively. Our findings highlight the structural integrity, antigenicity, and dense distribution on cell membrane of the vaccine-induced S proteins. Ad5-nCoV_O induced S proteins exhibit improved stability and reduced syncytia formation among inoculated cells. Our work demonstrates that Ad5-nCoV is a prominent platform for antigen induction and cryo-ET can be a useful technique for vaccine characterization and development.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"6 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653796","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

Next-generation small molecule inhibitors of clathrin function acutely inhibit endocytosis

IF 5.7 2区生物学

Structure Pub Date : 2025-03-19 DOI: 10.1016/j.str.2025.02.011

André Horatscheck, Michael Krauß, Haydar Bulut, Valerie Chambon, Massilullah Shafaq Zadah, Estelle Dransart, Kimberly Peloza, Karine F. Santos, Mark J. Robertson, Kate Prichard, Sandra Miksche, Silke Radetzki, Jens-Peter von Kries, Markus C. Wahl, Adam McCluskey, Ludger Johannes, Volker Haucke, Marc Nazaré

{"title":"Next-generation small molecule inhibitors of clathrin function acutely inhibit endocytosis","authors":"André Horatscheck, Michael Krauß, Haydar Bulut, Valerie Chambon, Massilullah Shafaq Zadah, Estelle Dransart, Kimberly Peloza, Karine F. Santos, Mark J. Robertson, Kate Prichard, Sandra Miksche, Silke Radetzki, Jens-Peter von Kries, Markus C. Wahl, Adam McCluskey, Ludger Johannes, Volker Haucke, Marc Nazaré","doi":"10.1016/j.str.2025.02.011","DOIUrl":"https://doi.org/10.1016/j.str.2025.02.011","url":null,"abstract":"Clathrin-mediated endocytosis (CME) is the predominant endocytic pathway in eukaryotic cells and a major regulator of cell physiology as it facilitates the internalization of receptors, channels, and transporters and viral entry. The clathrin terminal domain acts as a central protein interaction hub within the endocytic protein network. Previously described inhibitors of CME display off-target activities that result in cytotoxicity, providing limitations to their use. We report the development and characterization of next-generation small molecule inhibitors of clathrin terminal domain function. These compounds termed Pitstop 2c and Pitstop 2d occupy the binding site within the clathrin terminal domain for endocytic protein ligands including epsin, resulting in potent inhibition of receptor-mediated endocytosis and reduced entry of vesicular stomatitis virus (VSV) with minimal cytotoxic side effects. Next-generation Pitstops thus provide an improved toolset to address clathrin function in cell physiology with potential applications as inhibitors of virus and pathogen entry.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"32 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653800","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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