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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,4,2]]},"abstract":"<jats:p>\n                    Human gastric pathogen\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    (\n                    <jats:italic>H. pylori<\/jats:italic>\n                    ) is the primary risk factor for gastric cancer and is one of the most prevalent carcinogenic infectious agents. Vacuolating cytotoxin A (VacA) is a key virulence factor secreted by\n                    <jats:italic>H. pylori<\/jats:italic>\n                    and induces multiple cellular responses. Although structural and functional studies of VacA have been extensively performed, the high-resolution structure of a full-length VacA protomer and the molecular basis of its oligomerization are still unknown. Here, we use cryoelectron microscopy to resolve 10 structures of VacA assemblies, including monolayer (hexamer and heptamer) and bilayer (dodecamer, tridecamer, and tetradecamer) oligomers. The models of the 88-kDa full-length VacA protomer derived from the near-atomic resolution maps are highly conserved among different oligomers and show a continuous right-handed \u03b2-helix made up of two domains with extensive domain\u2013domain interactions. The specific interactions between adjacent protomers in the same layer stabilizing the oligomers are well resolved. For double-layer oligomers, we found short- and\/or long-range hydrophobic interactions between protomers across the two layers. Our structures and other previous observations lead to a mechanistic model wherein VacA hexamer would correspond to the prepore-forming state, and the N-terminal region of VacA responsible for the membrane insertion would undergo a large conformational change to bring the hydrophobic transmembrane region to the center of the oligomer for the membrane channel formation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1821959116","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T19:15:19Z","timestamp":1553109319000},"page":"6800-6805","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["Cryo-EM structures of\n                    <i>Helicobacter pylori<\/i>\n                    vacuolating cytotoxin A oligomeric assemblies at near-atomic resolution"],"prefix":"10.1073","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0414-4776","authenticated-orcid":false,"given":"Kaiming","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Bioengineering, James H. Clark Center, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huawei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7041-5960","authenticated-orcid":false,"given":"Shanshan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, James H. Clark Center, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigore D.","family":"Pintilie","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, James H. Clark Center, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tung-Chung","family":"Mou","sequence":"additional","affiliation":[{"name":"Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT 59812;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanzhu","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Sun Yat-Sen University, 510275 Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinfen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Sun Yat-Sen University, 510275 Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2358-841X","authenticated-orcid":false,"given":"Henry","family":"van den Bedem","sequence":"additional","affiliation":[{"name":"Biosciences Division, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025;"},{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Schmid","sequence":"additional","affiliation":[{"name":"CryoEM and Bioimaging Division, Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3573-9273","authenticated-orcid":false,"given":"Shannon Wing Ngor","family":"Au","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8910-3078","authenticated-orcid":false,"given":"Wah","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, James H. 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