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Title: Cryo-EM structures of Helicobacter pylori vacuolating cytotoxin A oligomeric assemblies at near-atomic resolution

Abstract

Helicobacter pylori infects nearly half of the world’s population and is the primary cause of various gastric diseases. It has evolved various virulence factors to aid its host colonization and infection, including the vacuolating cytotoxin A (VacA) that is responsible for the pathogenesis of H. pylori-related diseases. Here, we resolve multiple structures of the water-soluble VacA oligomeric assemblies using cryoelectron microscopy (cryo-EM) at near-atomic resolution. These studies suggest a model of structural changes of functional VacA hexamer needed for the pore-formation process across the membrane and highlight the capability of cryo-EM to resolve multiple structure snapshots from a single specimen at near-atomic resolution.

Authors:
ORCiD logo [1];  [2]; ORCiD logo [1];  [1];  [3];  [4];  [4]; ORCiD logo [5];  [6]; ORCiD logo [2]; ORCiD logo [7]
  1. Stanford Univ., Stanford, CA (United States)
  2. The Chinese Univ. of Hong Kong, Shatin (Hong Kong)
  3. Univ. of Montana, Missoula, MT (United States)
  4. Sun Yat-Sen Univ., Guangzhou (China)
  5. Stanford Univ., Menlo Park, CA (United States); Univ. of California, San Francisco, CA (United States)
  6. Stanford Univ., Menlo Park, CA (United States)
  7. Stanford Univ., Stanford, CA (United States); Stanford Univ., Menlo Park, CA (United States)
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1529236
Grant/Contract Number:  
AC02-76SF00515; P41GM103832; R01GM079429; S10OD021600; OIA-1738547
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 116; Journal Issue: 14; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; cryoelectron microscopy; Helicobacter pylori; vacuolating cytotoxin A; pore-forming toxin; oligomerization

Citation Formats

Zhang, Kaiming, Zhang, Huawei, Li, Shanshan, Pintilie, Grigore D., Mou, Tung -Chung, Gao, Yuanzhu, Zhang, Qinfen, van den Bedem, Henry, Schmid, Michael F., Au, Shannon Wing Ngor, and Chiu, Wah. Cryo-EM structures of Helicobacter pylori vacuolating cytotoxin A oligomeric assemblies at near-atomic resolution. United States: N. p., 2019. Web. doi:10.1073/pnas.1821959116.
Zhang, Kaiming, Zhang, Huawei, Li, Shanshan, Pintilie, Grigore D., Mou, Tung -Chung, Gao, Yuanzhu, Zhang, Qinfen, van den Bedem, Henry, Schmid, Michael F., Au, Shannon Wing Ngor, & Chiu, Wah. Cryo-EM structures of Helicobacter pylori vacuolating cytotoxin A oligomeric assemblies at near-atomic resolution. United States. doi:10.1073/pnas.1821959116.
Zhang, Kaiming, Zhang, Huawei, Li, Shanshan, Pintilie, Grigore D., Mou, Tung -Chung, Gao, Yuanzhu, Zhang, Qinfen, van den Bedem, Henry, Schmid, Michael F., Au, Shannon Wing Ngor, and Chiu, Wah. Wed . "Cryo-EM structures of Helicobacter pylori vacuolating cytotoxin A oligomeric assemblies at near-atomic resolution". United States. doi:10.1073/pnas.1821959116. https://www.osti.gov/servlets/purl/1529236.
@article{osti_1529236,
title = {Cryo-EM structures of Helicobacter pylori vacuolating cytotoxin A oligomeric assemblies at near-atomic resolution},
author = {Zhang, Kaiming and Zhang, Huawei and Li, Shanshan and Pintilie, Grigore D. and Mou, Tung -Chung and Gao, Yuanzhu and Zhang, Qinfen and van den Bedem, Henry and Schmid, Michael F. and Au, Shannon Wing Ngor and Chiu, Wah},
abstractNote = {Helicobacter pylori infects nearly half of the world’s population and is the primary cause of various gastric diseases. It has evolved various virulence factors to aid its host colonization and infection, including the vacuolating cytotoxin A (VacA) that is responsible for the pathogenesis of H. pylori-related diseases. Here, we resolve multiple structures of the water-soluble VacA oligomeric assemblies using cryoelectron microscopy (cryo-EM) at near-atomic resolution. These studies suggest a model of structural changes of functional VacA hexamer needed for the pore-formation process across the membrane and highlight the capability of cryo-EM to resolve multiple structure snapshots from a single specimen at near-atomic resolution.},
doi = {10.1073/pnas.1821959116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 14,
volume = 116,
place = {United States},
year = {2019},
month = {3}
}

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Cited by: 1 work
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Figures / Tables:

Fig. 1 Fig. 1: TenOAs of H. pylori VacA determined by cryoEM. The 2D class average and corresponding 3D reconstruction of each conformation are shown. OA-1 is the hexamer. OA-2a–f are all conformers of the dodecamer, having different relative rotational orientations between the two layers. OA-3 is the heptamer. OA-4 is themore » tetradecamer. OA-5 is the tridecamer. The percentages and resolutions in the last two rows refer to the final dataset and final maps.« less

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