Structure of the helicobacter pylori cag type IV secretion system

Jeong Min Chung, Michael J. Sheedlo, Anne M. Campbell, Neha Sawhney, Arwen E.Frick Cheng, Dana Borden Lacy, Timothy L. Cover, Melanie D. Ohi

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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 assembly, which we describe as three sub-assemblies: A 14-fold symmetric outer membrane core complex (OMCC), 17-fold symmetric periplasmic ring complex (PRC), and central stalk. 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 assemblies ever reported and illustrates the remarkable structural diversity that exists among bacterial T4SSs.

Original languageEnglish (US)
Article numbere47644
StatePublished - Jun 2019
Externally publishedYes

Bibliographical note

Funding Information:
We thank M Cianfrocco for cloud computing advice and M Su for imaging and data processing advice. We thank the Cianfrocco, Cover, Lacy, and Ohi labs for helpful discussions. We acknowledge the use of the U-M LSI cryo-EM facility, managed by M Su and A Bondy, and U-M LSI IT support. We also thank B Carragher and C Potter for support from the National Resource for Automated Molecular Microscopy located at the New York Structural Biology Center. This work was supported by NIH AI118932, CA116087, GM103310, and the Department of Veterans Affairs 1I01BX004447.

Funding Information:
This paper was supported by the following grants: National Institute of Allergy and Infectious Diseases AI118932 to Timothy L Cover, Melanie D Ohi. National Cancer Institute CA116087 to Timothy L Cover. U.S. Department of Veterans Affairs 1I01BX004447 to Timothy L Cover. National Institute of General Medical Sciences GM103310 to Melanie D Ohi.

Publisher Copyright:
© Chung et al.


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