DOI: 10.1128/mbio.02001-15. Molecular and Structural Analysis of the Helicobacter pylori <i>cag</i> Type IV Secretion System Core Complex

Molecular and Structural Analysis of the Helicobacter pylori cag Type IV Secretion System Core Complex

10.1128/mbio.02001-15

Crossref journal-article

American Society for Microbiology

mBio (235)

Abstract

ABSTRACT Bacterial type IV secretion systems (T4SSs) can function to export or import DNA, and can deliver effector proteins into a wide range of target cells. Relatively little is known about the structural organization of T4SSs that secrete effector proteins. In this report, we describe the isolation and analysis of a membrane-spanning core complex from the Helicobacter pylori cag T4SS, which has an important role in the pathogenesis of gastric cancer. We show that this complex contains five H. pylori proteins, CagM, CagT, Cag3, CagX, and CagY, each of which is required for cag T4SS activity. CagX and CagY are orthologous to the VirB9 and VirB10 components of T4SSs in other bacterial species, and the other three Cag proteins are unique to H. pylori . Negative stain single-particle electron microscopy revealed complexes 41 nm in diameter, characterized by a 19-nm-diameter central ring linked to an outer ring by spoke-like linkers. Incomplete complexes formed by Δ cag3 or Δ cagT mutants retain the 19-nm-diameter ring but lack an organized outer ring. Immunogold labeling studies confirm that Cag3 is a peripheral component of the complex. The cag T4SS core complex has an overall diameter and structural organization that differ considerably from the corresponding features of conjugative T4SSs. These results highlight specialized features of the H. pylori cag T4SS that are optimized for function in the human gastric mucosal environment. IMPORTANCE Type IV secretion systems (T4SSs) are versatile macromolecular machines that are present in many bacterial species. In this study, we investigated a T4SS found in the bacterium Helicobacter pylori . H. pylori is an important cause of stomach cancer, and the H. pylori T4SS contributes to cancer pathogenesis by mediating entry of CagA (an effector protein regarded as a “bacterial oncoprotein”) into gastric epithelial cells. We isolated and analyzed the membrane-spanning core complex of the H. pylori T4SS and showed that it contains unique proteins unrelated to components of T4SSs in other bacterial species. These results constitute the first structural analysis of the core complex from this important secretion system.

Bibliography

Frick-Cheng, A. E., Pyburn, T. M., Voss, B. J., McDonald, W. H., Ohi, M. D., & Cover, T. L. (2016). Molecular and Structural Analysis of the Helicobacter pylori cag Type IV Secretion System Core Complex. MBio, 7(1).

Authors 6

Arwen E. Frick-Cheng (first)
Tasia M. Pyburn (additional)
Bradley J. Voss (additional)
W. Hayes McDonald (additional)
Melanie D. Ohi (additional)
Timothy L. Cover (additional)

References 47 Referenced 101

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Dates

Type	When
Created	9 years, 7 months ago (Jan. 13, 2016, 1:57 p.m.)
Deposited	3 years, 5 months ago (March 7, 2022, 9:05 p.m.)
Indexed	18 hours, 34 minutes ago (Aug. 21, 2025, 1:52 p.m.)
Issued	9 years, 5 months ago (March 2, 2016)
Published	9 years, 5 months ago (March 2, 2016)
Published Print	9 years, 5 months ago (March 2, 2016)

Funders 4

HHS | National Institutes of Health 10.13039/100000002 National Institutes of Health
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards2
1. AI039657
2. CA116087
HHS | National Institutes of Health 10.13039/100000002 National Institutes of Health
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. F31 AI112324
HHS | National Institutes of Health 10.13039/100000002 National Institutes of Health
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. T32 AI007281
U.S. Department of Veterans Affairs 10.13039/100000738
Region: Americas
gov (National government)
Labels8
1. Department of Veterans Affairs
2. United States Department of Veterans Affairs
3. US Department of Veterans Affairs
4. U.S. Dept. of Veterans Affairs
5. Veterans Affairs
6. Veterans Affairs Department
7. VA
8. USDVA
Awards1
1. 2I01BX000627

BibTeX

@article{Frick_Cheng_2016, title={Molecular and Structural Analysis of the Helicobacter pylori cag Type IV Secretion System Core Complex}, volume={7}, ISSN={2150-7511}, url={http://dx.doi.org/10.1128/mbio.02001-15}, DOI={10.1128/mbio.02001-15}, number={1}, journal={mBio}, publisher={American Society for Microbiology}, author={Frick-Cheng, Arwen E. and Pyburn, Tasia M. and Voss, Bradley J. and McDonald, W. Hayes and Ohi, Melanie D. and Cover, Timothy L.}, editor={Blaser, Martin J.}, year={2016}, month=mar }

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