Cryo-EM reveals species-specific components within the helicobacter pylori cag type IV secretion system core complex

Michael J. Sheedlo, Jeong Min Chung, Neha Sawhney, Clarissa L. Durie, Timothy L. Cover, Melanie D. Ohi, D. Borden Lacy

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The pathogenesis of Helicobacter pylori-associated gastric cancer is dependent on delivery of CagA into host cells through a type IV secretion system (T4SS). The H. pylori Cag T4SS includes a large membrane-spanning core complex containing five proteins, organized into an outer membrane cap (OMC), a periplasmic ring (PR) and a stalk. Here, we report cryo-EM reconstructions of a core complex lacking Cag3 and an improved map of the wild-type complex. We define the structures of two unique species-specific components (Cag3 and CagM) and show that Cag3 is structurally similar to CagT. Unexpectedly, components of the OMC are organized in a 1:1:2:2:5 molar ratio (CagY:CagX:CagT:CagM:Cag3). CagX and CagY are components of both the OMC and the PR and bridge the symmetry mismatch between these regions. These results reveal that assembly of the H. pylori T4SS core complex is dependent on incorporation of interwoven species-specific components.

Original languageEnglish (US)
Article numbere59495
Pages (from-to)1-22
Number of pages22
JournaleLife
Volume9
DOIs
StatePublished - Sep 2020
Externally publishedYes

Bibliographical note

Funding Information:
We acknowledge the use of the University of Michigan cryo-EM facility, managed by M Su, A Bondy, and L Koepping, U-M LSI IT, and LSI and U-M BSI support. The work presented here was supported by NIH AI118932, CA116087, AI039657, GM103310, NIH 2T32DK007673, S10OD020011, and the Department of Veterans Affairs 5I01BX004447. A portion of the molecular graphics and analyses was performed with UCSF Chimera and ChimeraX developed by the Resource for Biocomputing, Visualization, and Informatics at UC-San Francisco, with support from NIH P41-GM103311. National Institute of Allergy and Infectious Diseases AI118932 Timothy L Cover Melanie D Ohi D Borden Lacy. National Institute of Allergy and Infectious Diseases AI039657 Timothy L Cover. National Cancer Institute CA116087 Timothy L Cover. National Institute of General Medical Sciences GM103310 Melanie D Ohi. National Institute of Diabetes and Digestive and Kidney Diseases 2T32DK007673 Michael J Sheedlo.National Institutes of Health S10OD020011 Melanie D Ohi. U.S. Department of Veterans Affairs 5I01BX004447 Timothy L Cover.

Funding Information:
We acknowledge the use of the University of Michigan cryo-EM facility, managed by M Su, A Bondy, and L Koepping, U-M LSI IT, and LSI and U-M BSI support. The work presented here was supported by NIH AI118932, CA116087, AI039657, GM103310, NIH 2T32DK007673, S10OD020011, and the Department of Veterans Affairs 5I01BX004447. A portion of the molecular graphics and analyses was performed with UCSF Chimera and ChimeraX developed by the Resource for Biocomputing, Visualization, and Informatics at UC-San Francisco, with support from NIH P41-GM103311.

Publisher Copyright:
© 2020, eLife Sciences Publications Ltd. All rights reserved.

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