{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T20:08:08Z","timestamp":1776024488498,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1008169","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000}}],"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation of Knut and Alice Wallenberg","award":["2016.0023"],"award-info":[{"award-number":["2016.0023"]}]},{"name":"Foundation of Knut and Alice Wallenberg","award":["2016.0023"],"award-info":[{"award-number":["2016.0023"]}]},{"name":"Foundation of Knut and Alice Wallenberg","award":["2019.0353"],"award-info":[{"award-number":["2019.0353"]}]},{"name":"Foundation of Knut and Alice Wallenberg","award":["2019.0353"],"award-info":[{"award-number":["2019.0353"]}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["P2ZHP3_191289"],"award-info":[{"award-number":["P2ZHP3_191289"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002915","name":"The Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["Equipe FRM 2017M.DEQ20170839114"],"award-info":[{"award-number":["Equipe FRM 2017M.DEQ20170839114"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002915","name":"The Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["Equipe FRM 2017M.DEQ20170839114"],"award-info":[{"award-number":["Equipe FRM 2017M.DEQ20170839114"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["765042"],"award-info":[{"award-number":["765042"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    <jats:italic>Streptococcus pyogenes<\/jats:italic>\n                    (Group A streptococcus; GAS) is an important human pathogen responsible for mild to severe, life-threatening infections. GAS expresses a wide range of virulence factors, including the M family proteins. The M proteins allow the bacteria to evade parts of the human immune defenses by triggering the formation of a dense coat of plasma proteins surrounding the bacteria, including IgGs. However, the molecular level details of the M1-IgG interaction have remained unclear. Here, we characterized the structure and dynamics of this interaction interface in human plasma on the surface of live bacteria using integrative structural biology, combining cross-linking mass spectrometry and molecular dynamics (MD) simulations. We show that the primary interaction is formed between the S-domain of M1 and the conserved IgG Fc-domain. In addition, we show evidence for a so far uncharacterized interaction between the A-domain and the IgG Fc-domain. Both these interactions mimic the protein G-IgG interface of group C and G streptococcus. These findings underline a conserved scavenging mechanism used by GAS surface proteins that block the IgG-receptor (Fc\u03b3R) to inhibit phagocytic killing. We additionally show that we can capture Fab-bound IgGs in a complex background and identify XLs between the constant region of the Fab-domain and certain regions of the M1 protein engaged in the Fab-mediated binding. Our results elucidate the M1-IgG interaction network involved in inhibition of phagocytosis and reveal important M1 peptides that can be further investigated as future vaccine targets.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1008169","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T18:45:40Z","timestamp":1610045140000},"page":"e1008169","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Structural determination of Streptococcus pyogenes M1 protein interactions with human immunoglobulin G using integrative structural biology"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-0650","authenticated-orcid":true,"given":"Hamed","family":"Khakzad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5922-4549","authenticated-orcid":true,"given":"Lotta","family":"Happonen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8413-2665","authenticated-orcid":true,"given":"Yasaman","family":"Karami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sounak","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9719-6609","authenticated-orcid":true,"given":"Gizem Ert\u00fcrk","family":"Bergdahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-8092","authenticated-orcid":true,"given":"Michael","family":"Nilges","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Tran Van Nhieu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2889-7169","authenticated-orcid":true,"given":"Johan","family":"Malmstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9885-9312","authenticated-orcid":true,"given":"Lars","family":"Malmstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"issue":"3","key":"pcbi.1008169.ref001","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrmicro771","article-title":"The pathogenesis of streptococcal infections: from tooth decay to meningitis","volume":"1","author":"TJ Mitchell","year":"2003","journal-title":"Nat Rev Microbiol"},{"key":"pcbi.1008169.ref002","first-page":"1","article-title":"Group a streptococcal diseases and their global burden","volume":"368","author":"AP Ralph","year":"2013","journal-title":"Curr Top Microbiol Immunol"},{"issue":"26","key":"pcbi.1008169.ref003","doi-asserted-by":"crossref","first-page":"18175","DOI":"10.1074\/jbc.M114.565978","article-title":"Functional and structural properties of a novel protein and virulence factor (Protein sHIP) in Streptococcus pyogenes.","volume":"289","author":"M Wisniewska","year":"2014","journal-title":"J Biol Chem"},{"issue":"1","key":"pcbi.1008169.ref004","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1038\/s41467-019-10583-5","article-title":"A quantitative Streptococcus pyogenes-human protein-protein interaction map reveals localization of opsonizing antibodies.","volume":"10","author":"L Happonen","year":"2019","journal-title":"Nat Commun"},{"issue":"3","key":"pcbi.1008169.ref005","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s00430-020-00663-5","article-title":"Structural proteomics, electron cryo-microscopy and structural modeling approaches in bacteria-human protein interactions","volume":"209","author":"S Chowdhury","journal-title":"Med Microbiol Immunol"},{"issue":"7","key":"pcbi.1008169.ref006","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1093\/emboj\/21.7.1607","article-title":"IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G","volume":"21","author":"U von Pawel-Rammingen","year":"2002","journal-title":"EMBO J"},{"issue":"12","key":"pcbi.1008169.ref007","doi-asserted-by":"crossref","first-page":"3046","DOI":"10.1093\/emboj\/20.12.3046","article-title":"EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG","volume":"20","author":"M Collin","year":"2001","journal-title":"EMBO J"},{"issue":"1","key":"pcbi.1008169.ref008","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1042\/BJ20130126","article-title":"EndoS2 is a unique and conserved enzyme of serotype M49 group A Streptococcus that hydrolyses N-linked glycans on IgG and \u03b11-acid glycoprotein","volume":"455","author":"J Sj\u00f6gren","year":"2013","journal-title":"Biochem J"},{"issue":"2","key":"pcbi.1008169.ref009","doi-asserted-by":"crossref","first-page":"969","DOI":"10.4049\/jimmunol.133.2.969","article-title":"Purification and some properties of streptococcal protein G, a novel IgG-binding reagent","volume":"133","author":"L Bj\u00f6rck","year":"1984","journal-title":"J Immunol"},{"issue":"6","key":"pcbi.1008169.ref010","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.4049\/jimmunol.132.6.3091","article-title":"Streptococcal Fc receptors. 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Karami","year":"2018","journal-title":"Sci Rep"},{"issue":"3","key":"pcbi.1008169.ref032","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0969-2126(01)00157-5","article-title":"Crystal structure of the C2 fragment of streptococcal protein G in complex with the Fc domain of human IgG","volume":"3","author":"AE Sauer-Eriksson","year":"1995","journal-title":"Structure"},{"issue":"4","key":"pcbi.1008169.ref033","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.4049\/jimmunol.135.4.2589","article-title":"Protein G: a powerful tool for binding and detection of monoclonal and polyclonal antibodies","volume":"135","author":"B Akerstr\u00f6m","year":"1985","journal-title":"J Immunol"},{"issue":"9","key":"pcbi.1008169.ref034","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1021\/bi00512a001","article-title":"Crystallographic refinement and atomic models of a human Fc fragment and its complex with fragment B of protein A from Staphylococcus aureus at 2.9- and 2.8-A resolution","volume":"20","author":"J. Deisenhofer","year":"1981","journal-title":"Biochemistry"},{"issue":"Suppl 4","key":"pcbi.1008169.ref035","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12859-019-2686-8","article-title":"Greedy de novo motif discovery to construct motif repositories for bacterial proteomes","volume":"20","author":"H Khakzad","year":"2019","journal-title":"BMC Bioinformatics"},{"issue":"5","key":"pcbi.1008169.ref036","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/mbo3.278","article-title":"Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein.","volume":"4","author":"J Lannerg\u00e5rd","year":"2015","journal-title":"Microbiologyopen"},{"issue":"2","key":"pcbi.1008169.ref037","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1006\/abio.2001.5119","article-title":"BIACORE data processing: an evaluation of the global fitting procedure","volume":"293","author":"MB Khalifa","year":"2001","journal-title":"Anal Biochem"},{"issue":"8","key":"pcbi.1008169.ref038","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1080\/21645515.2018.1462427","article-title":"Contribution of cryptic epitopes in designing a group A streptococcal vaccine","volume":"14","author":"V Ozberk","year":"2018","journal-title":"Hum Vaccin Immunother"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1008169","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008169","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T01:45:23Z","timestamp":1697507123000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008169"}},"subtitle":[],"editor":[{"given":"Alexey","family":"Onufriev","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,7]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1008169","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.07.21.213652","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,7]]}}}