Rho GTPase Recognition Mechanism of ADP-ribosylating C3 exoenzyme
| Project/Area Number |
15K08289
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Kyoto Sangyo University |
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Principal Investigator |
TSUGE Hideaki 京都産業大学, 総合生命科学部, 教授 (40299342)
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| Research Collaborator |
YOSHIDA Toru 京都産業大学, 総合生命科学部, 研究助教 (30724546)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | ADPリボシル化 / 基質特異性 / C3 / RhoA / Cdc42 / タンパク質複合体 / X線結晶構造解析 / Ia / 基質タンパク質認識機構 / 修飾アミノ酸認識機構 / アクチン / 細菌毒素 / 基質タンパク質認識 / CPILE-a / Rac1 / 複合体 / 構造酵素学 |
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| Outline of Final Research Achievements |
C3 exoenzyme is a mono-ADP-ribosyltransferase (ART) that catalyzes transfer of an ADP-ribose moiety from NAD(+) to Rho GTPases. C3 has long been used to study the diverse regulatory functions of Rho GTPases. How C3 recognizes its substrate and how ADP-ribosylation proceeds are still poorly understood. We determined the crystal structure of the C3 exoenzyme-RhoA complex. It reveals that C3 recognizes RhoA via the switch I, switch II, and interswitch regions. In C3-RhoA(GTP) and C3-RhoA(GDP), switch I and II adopt the GDP and GTP conformations, respectively, which explains why C3 can ADP-ribosylate both nucleotide forms. Based on structural information, we successfully changed Cdc42 to an active substrate with combined mutations in the C3-Rho GTPase interface. The structure shows directly for the first time that the ARTT loop is the key to target protein recognition, and they also serve to bridge the gaps among independent studies of Rho GTPases and C3.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Crystal structure and structure-based mutagenesis of actin-specific ADP-ribosylating toxin CPILE-a as novel enterotoxin.2017
Author(s)
Toniti, W., Yoshida, T., Tsurumura, T., Irikura, D., Monma, C., Kamata, Y., and Tsuge, H.
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Journal Title
PLoS ONE
Volume: 12
Issue: 2
Pages: e0171278-e0171278
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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