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.

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Published in Cell Reports, v. 23, issue 3, p. 673-681.

© 2018 The Authors.

This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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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.

Related Content

Detailed methods of electron cryotomography sample preparation, data collection, and data processing are outlined in the Supplemental Experimental Procedures.

The accession numbers for the sub-tomogram averages of cag T4SS machinery that support the findings of this study are EMDB: 7474 (aligned on the periplasmic region) and EMDB: 7475 (aligned on the cytoplasmic region).

Supplemental Information includes Supplemental Experimental Procedures and four figures and can be found with this article online at https://doi.org/10.1016/j.celrep.2018.03.085.

1-s2.0-S2211124718304467-mmc1.pdf (4114 kB)
Document S1. Supplemental Experimental Procedures and Figures S1–S4.

1-s2.0-S2211124718304467-mmc2.pdf (7999 kB)
Document S2. Article plus Supplemental Information.