Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex
- Vanderbilt University Medical Center, United States
- University of Michigan, United States
- Vanderbilt University School of Medicine, United States
- University Of Michigan, United States
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 5 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.
Data availability
All cryo-EM data included in this manuscript are available through the Electron Microscopy Data Bank (EMD-20021, EMD-22081, EMD-22076, and EMD-22077). All models that were constructed from these data are available via the Protein Data Bank (PDB 6X6S, 6X6J, 6X6K, and 6X6L).
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Cryo-EM Structure of the Helicobacter pylori OMCProtein Data Bank, 6X6S.
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Funding
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
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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