Structural Study on Mental Disease Gene Product Protein

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06980
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Hosei University (2016-2017); Yokohama City University (2015)
• Principal Investigator: UNZAI Satoru 法政大学, 生命科学部, 准教授 (60336592)
• Co-Investigator(Renkei-kenkyūsha): PARK Sam-Yong 横浜市立大学, 生命医科学研究科, 教授 (20291932)
• Research Collaborator: KOMIYAMA Noboru The University of Edinburgh, Centre for Clinical Brain Sciences, Senior Lecturer
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: タンパク質 / 結晶構造解析

Outline of Final Research Achievements

The brain-specific synaptic GTPase activating protein (SynGAP) is important in synaptic plasticity. Mutations in SYNGAP1 gene cause epileptic encephalopathy, intellectual disability, and autism via haploinsufficiency. Basic research is needed to better understand the molecular functions of the SynGAP protein, which will lead to targets for therapeutic intervention. Structural biology methods were applied for the SynGAP function research. Recombinant SynGAP and Rap1B (SynGAP can enhance Rap1B GTPase activity) were prepared using e-coli expression system. We succeeded in solving high resolution crystal structure of the Rap1B protein and understanding its molecular switch mechanism. We established small volume GTPase activity measurement system using malachite green. Rap1B GTPase activity enhancement by SynGAP can be detected by this system.

Free Research Field

構造生物学