Elucidation of regulatory mechanism of RhoGEF by multidomains cooperation
| Project/Area Number |
15K06987
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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 |
Structural biochemistry
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Kukimoto Mutsuko 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, 上級研究員 (30321756)
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| Co-Investigator(Kenkyū-buntansha) |
村山 和隆 東北大学, 医工学研究科, 准教授 (40400452)
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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 |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | X線結晶構造解析 / シグナル伝達 / Gタンパク質 / Rhoファミリー / グアニンヌクレオチド交換因子 / 低分子量Gタンパク質 / 結晶構造解析 / X線結晶解析 |
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| Outline of Final Research Achievements |
In this study, we aimed to elucidate the activation regulation mechanism of RhoGEF proteins by GEF domain and other functional domains by analyzing their structure in full length or multidomain state. By dynamic light scattering and ultracentrifugation analysis, we found that intersectin 2 has multiple SH3 domains and DH-PH domains connected by a flexible loop, and acquires the structural freedom as a whole molecule. We also found that DOCK5 forms a stable complex with the regulatory protein ELMO1, takes up an extended structure, and binds to Rac1 on the side of the molecule. Finally, X-ray crystal structure analysis revealed structural changes of the DOCK7 DHR-2 domain in G protein binding.
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Targeting Ras-driven cancer cell survival and invasion through selective inhibition of DOCK12017
Author(s)
Tajiri H, Uruno T, Shirai T, Takaya D, Matsunaga S, Setoyama D, Watanabe M, Kukimoto-Niino M, Oisaki K, Ushijima M, Sanematsu F, Honma T, Terada T, Oki E, Shirasawa S, Maehara Y, Kang D, Cote J-F, Yokoyama S, Kanai M, Fukui Y
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Journal Title
Cell Reports
Volume: 19
Issue: 5
Pages: 969-980
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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