Structure of the Helicobacter pylori Cag Type IV secretion system
- University of Michigan, United States
- Vanderbilt University School of Medicine, United States
Abstract
Bacterial type IV secretion systems (T4SSs) are molecular machines that can mediate interbacterial DNA transfer through conjugation and delivery of effector molecules into host cells. The Helicobacter pylori Cag T4SS translocates CagA, a bacterial oncoprotein, into gastric cells, contributing to gastric cancer pathogenesis. We report the structure of a membrane-spanning Cag T4SS complex, which contains three sub-complexes: a 14-fold symmetric outer membrane core complex (OMCC), 17-fold symmetric periplasmic ring complex (PRC), and stalk domain. Features that differ markedly from those of prototypical T4SSs include an expanded OMCC and unexpected symmetry mismatch between the OMCC and PRC. This structure is one of the largest bacterial secretion system complexes ever reported and illustrates the remarkable structural diversity that exists among bacterial T4SSs.
Data availability
The cryo-EM volumes have been deposited in the Electron Microscopy Data Bank under accession codes EMD-20023 (T4SS C1 reconstruction), EMD-20020 (Focused OMCC Reconstruction), EMD-20022 (OMCC Asymmetric Reconstruction), EMD-20021 (Focused PRC Reconstruction). Map coordinates have been deposited in the Protein Data Bank under accession numbers 6OEE (CagT), 6OEG (CagX), and 6ODI (CagY), 6OEF (O-layer), 6OEH (I-Layer), and 6ODJ (PRC).
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T4SS C1 reconstructionElectron Microscopy Data Bank, EMD-20023.
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Focused OMCC ReconstructionElectron Microscopy Data Bank, EMD-20020.
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OMCC Asymmetric ReconstructionElectron Microscopy Data Bank, EMD-20022.
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Focused PRC ReconstructionElectron Microscopy Data Bank, EMD-20021.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (AI118932)
- Timothy L Cover
- Melanie D Ohi
National Cancer Institute (CA116087)
- Timothy L Cover
Department of Veterans' Affairs (1I01BX004447)
- Timothy L Cover
National Institute of General Medical Sciences (GM103310)
- Melanie D Ohi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Chung et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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