第1292回生物科学セミナー
Structural and conformational transitions in the neurotensin receptor 1-Gi1 protein complex
加藤 英明 先生（東京大学 大学院総合文化研究科 先進科学研究機構 准教授（大学院総合文化研究科 広域科学専攻 生命環境科学系 准教授））
2019年07月16日(火) 16:00-17:00 理学部1号館東棟 380号室
The neurotensin receptor 1 (NTSR1) is a G-protein-coupled receptor (GPCR) involved in regulation of blood pressure, body temperature, weight, and response to pain. NTSR1 couples to multiple G-protein subtypes, but the molecular details of G-protein activation remain unknown. In this seminar, I will present 3-Å structures of the human NTSR1 in complex with the heterotrimeric Gi1 protein in two distinct conformations (C and NC state). While the C-state complex is similar to recently reported GPCR-Gi/o complexes, the G-protein in the NC state is rotated by ~45 degrees relative to the receptor. NTSR1 in the NC state exhibits features of both active and inactive conformations, suggesting that the structure represents an intermediate along the G-protein activation pathway. This structural information, complemented by molecular dynamics simulations and functional studies, provide insights into the complex process of G-protein activation.
