2010 Fiscal Year Final Research Report
Structure-based analysis of biological activity of Helicobacter pylori CagA
| Project/Area Number |
20390089
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
HIGASHI Hideaki Hokkaido University, 人獣共通感染症リサーチセンター, 教授 (20311227)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 胃がん / チロシンフォスファターゼ / 分子立体構造 / ピロリ菌 / チロシンリン酸化 |
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| Research Abstract |
Helicobacter pylori CagA protein is injected into gastric epithelial cells, where it interacts with cellular proteins such as SHP-2 and Par1 through its C-terminal region containing Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. Consequently, CagA perturbs intracellular machineries involved in the regulation of cell growth and cell polarity. To elucidate molecular basis for the pathophysiological activity of CagA, we sought to determine three-dimensional structure of CagA. We performed a limited proteolysis experiment of CagA and identified a specific cleavage site, which could represent a linker region that connects the possible N-terminal and C-terminal structural domains of CagA. Intriguingly, the C-terminal proteolytic fragment of CagA was bound to the remaining N-terminal proteolytic fragment. Furthermore, we found that N-terminal fragment enhances CagA biological activity that induces cell morphological changes in depending on the C-terminal region of CagA. Our finding indicates that an intramolecular interaction between the N-terminal and C-terminal domains plays an important role in the structural integrity of the biologically active CagA protein.
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Research Products
(13 results)
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[Journal Article] Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse.2008
Author(s)
Ohnishi N., Yuasa H., Tanaka S., Sawa H., Miura M., Matsui A., Higashi H., Musashi M., Iwabuchi K., Suzuki M., Yamada G., Azuma T., Hatakeyama M.
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Journal Title
Proc. Natl. Acad. Sci. USA. 105
Pages: 1003-1008
Peer Reviewed
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