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2017 Fiscal Year Final Research Report

Elucidation of regulatory mechanism of RhoGEF by multidomains cooperation

Research Project

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Project/Area Number 15K06987
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Structural biochemistry
Research InstitutionInstitute of Physical and Chemical Research

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)

Co-Investigator(Kenkyū-buntansha) 村山 和隆  東北大学, 医工学研究科, 准教授 (40400452)
Project Period (FY) 2015-04-01 – 2018-03-31
KeywordsX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
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.

Free Research Field

X線結晶構造解析

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Published: 2019-03-29  

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