{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:32:40Z","timestamp":1790400760084,"version":"4.1.0"},"reference-count":88,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,7,8]],"date-time":"2016-07-08T00:00:00Z","timestamp":1467936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:italic>Helicobacter pylori<\/jats:italic> colonizes the human stomach and is a potential cause of peptic ulceration or gastric adenocarcinoma. <jats:italic>H. pylori<\/jats:italic> secretes a pore\u2010forming toxin known as vacuolating cytotoxin A (VacA). The 88 kDa secreted VacA protein, composed of an N\u2010terminal p33 domain and a C\u2010terminal p55 domain, assembles into water\u2010soluble oligomers. The structural organization of membrane\u2010bound VacA has not been characterized in any detail and the role(s) of specific VacA domains in membrane binding and insertion are unclear. We show that membrane\u2010bound VacA organizes into hexameric oligomers. Comparison of the two\u2010dimensional averages of membrane\u2010bound and soluble VacA hexamers generated using single particle electron microscopy reveals a structural difference in the central region of the oligomers (corresponding to the p33 domain), suggesting that membrane association triggers a structural change in the p33 domain. Analyses of the isolated p55 domain and VacA variants demonstrate that while the p55 domain can bind membranes, the p33 domain is required for membrane insertion. Surprisingly, neither VacA oligomerization nor the presence of putative transmembrane GXXXG repeats in the p33 domain is required for membrane insertion. These findings provide new insights into the process by which VacA binds and inserts into the lipid bilayer to form membrane channels.<\/jats:p>","DOI":"10.1111\/mmi.13443","type":"journal-article","created":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T00:58:31Z","timestamp":1466125111000},"page":"22-36","source":"Crossref","is-referenced-by-count":21,"title":["Structural organization of membrane\u2010inserted hexamers formed by <i>Helicobacter pylori<\/i> VacA toxin"],"prefix":"10.1111","volume":"102","author":[{"given":"Tasia M.","family":"Pyburn","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology Vanderbilt University School of Medicine Nashville TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora J.","family":"Foegeding","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Vanderbilt University School of Medicine Nashville TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gonz\u00e1lez\u2010Rivera","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology Vanderbilt University School of Medicine Nashville TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan A.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Vanderbilt University School of Medicine Nashville TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen L.","family":"Gould","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Vanderbilt University School of Medicine Nashville TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy L.","family":"Cover","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology Vanderbilt University School of Medicine Nashville TN 37232"},{"name":"Department of Medicine Vanderbilt University School of Medicine Nashville TN 37232"},{"name":"Veterans Affairs Tennessee Valley Healthcare System Nashville TN 37212"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie D.","family":"Ohi","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Vanderbilt University School of Medicine Nashville TN 37232"},{"name":"Center for Structural Biology, Vanderbilt University School of Medicine Nashville TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)00047-5"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.11.009"},{"key":"e_1_2_6_4_1","unstructured":"Anonymous(1994). 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