Structure of the Helicobacter pylori CagA oncoprotein bound to the human tumor suppressor ASPP2
10.1073/pnas.1320631111
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

Significance Helicobacter pylori is the greatest risk factor for gastric adenocarcinoma and has been classified as a carcinogen by the World Health Organization. Cytotoxin associated gene A (CagA) is the primary virulence determinant of H. pylori and is sufficient to induce tumor formation in animal models. We show here that the host tumor suppressor Apoptosis-stimulating Protein of p53-2 (ASPP2) binds robustly to an N-terminal domain of CagA and elucidate the crystal structure of this complex, revealing the details of the CagA–ASPP2 interaction. Structure-based mutagenesis disrupts this complex in vitro and in cells. Furthermore, we show that the CagA–ASPP2 interaction modulates critical ASPP2 functions, such as p53-binding and apoptosis of H. pylori -infected cells.

Bibliography

Nešić, D., Buti, L., Lu, X., & Stebbins, C. E. (2014). Structure of the Helicobacter pylori CagA oncoprotein bound to the human tumor suppressor ASPP2. Proceedings of the National Academy of Sciences, 111(4), 1562–1567.

Authors 4
  1. Dragana Nešić (first)
  2. Ludovico Buti (additional)
  3. Xin Lu (additional)
  4. C. Erec Stebbins (additional)
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Dates
Type When
Created 11 years, 7 months ago (Jan. 13, 2014, 9:39 p.m.)
Deposited 3 years, 2 months ago (June 7, 2022, 8:09 a.m.)
Indexed 3 months, 3 weeks ago (May 1, 2025, 11:44 a.m.)
Issued 11 years, 7 months ago (Jan. 13, 2014)
Published 11 years, 7 months ago (Jan. 13, 2014)
Published Online 11 years, 7 months ago (Jan. 13, 2014)
Published Print 11 years, 7 months ago (Jan. 28, 2014)
Funders 0

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@article{Ne_i__2014, title={Structure of the Helicobacter pylori CagA oncoprotein bound to the human tumor suppressor ASPP2}, volume={111}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1320631111}, DOI={10.1073/pnas.1320631111}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Nešić, Dragana and Buti, Ludovico and Lu, Xin and Stebbins, C. Erec}, year={2014}, month=jan, pages={1562–1567} }