Abstract
The type IV secretion system (T4SS) is a versatile nanomachine that translocates diverse effector molecules between microbes and into eukaryotic cells. Here, using electron cryotomography, we reveal the molecular architecture of the Helicobacter pylori cag T4SS. Although most components are unique to H. pylori, the cag T4SS exhibits remarkable architectural similarity to other T4SSs. Our images revealed that, when H. pylori encounters host cells, the bacterium elaborates membranous tubes perforated by lateral ports. Sub-tomogram averaging of the cag T4SS machinery revealed periplasmic densities associated with the outer membrane, a central stalk, and peripheral wing-like densities. Additionally, we resolved pilus-like rod structures extending from the cag T4SS into the inner membrane, as well as densities within the cytoplasmic apparatus corresponding to a short central barrel surrounded by four longer barrels. Collectively, these studies reveal the structure of a dynamic molecular machine that evolved to function in the human gastric niche. Bacteria assemble specialized type IV secretion systems (T4SSs) to inject molecular cargo into target cells. Using electron cryotomography, Chang and Shaffer et al. report the first structure of a cancer-associated T4SS in vivo and describe unique membranous appendages that are produced when H. pylori encounters gastric epithelial cells.
Original language | English |
---|---|
Pages (from-to) | 673-681 |
Number of pages | 9 |
Journal | Cell Reports |
Volume | 23 |
Issue number | 3 |
DOIs | |
State | Published - Apr 17 2018 |
Bibliographical note
Funding Information:We thank Dr. Tim Cover for providing H. pylori strains and Dr. Joseph Vogel and Dr. Maria Hadjifrangiskou for helpful discussions. This work was supported by NIH grant R01 AI127401 to G.J.J., NIH grant F32 DK105720 to C.L.S., NIH grant T32 A1007474 to C.L.S., and the Burroughs Wellcome Fund 2016 Collaborative Research Travel Grant 1016383 to C.L.S.
Publisher Copyright:
© 2018 The Authors
Keywords
- CagA
- Helicobacter pylori
- bacterial molecular machines
- cryo-ET
- electron cryotomography
- gastric cancer
- host-pathogen interaction
- subtomogram averaging
- type IV secretion system
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)