Reconstruction of signal transduction machinary in the cell membrane

2018 Fiscal Year Final Research Report

• Project/Area Number: 15KT0087
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Constructive Systems Biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Sako Yasushi 国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (20215700)
• Project Period (FY): 2015-07-10 – 2019-03-31
• Keywords: シグナル伝達 / ナノマシン

Outline of Final Research Achievements

We have developed reconstitution membrane of EGF receptor (EGFR) for analyzing molecular mechanism of signal transduction across the plasma membrane. EGFR molecules were incorporated into nanodiscs with the diameter of 10-15 nm. Single-molecule FRET imaging of the transmembrane (TM)-juxtamenbrane (JM) domains of EGFR revealed that dimerization of EGFR, which is responsible for signal transduction, is induced by interactions of the JM domain with acidic membrane lipids, and inhibitory effect of the phosphorylation at the JM domain for dimerization requires acidic lipids in the membrane. Cholesterol in the membrane also induced dimerization of EGFR, however, dimer structures suggested to be different from that in membranes without cholesterol.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

細胞膜受容体は細胞内外の情報変換を行う重要な蛋白質分子であるが、膜を介した情報伝達は信号分子と受容体の相互作用、受容体の分子構造・会合状態変化、受容体と細胞質分子の相互作用などが、さらに複雑かつ不均一な膜構造・膜脂質組成と絡み合って起こる複雑な反応である。ナノディスクは反応要素を最も小数・単純化できる再構成系であり、リポソームなど再構成膜系を利用した構成的システム研究へ基盤情報を与えることができる。本研究では蛋白質と脂質の協調が反応医御に必要であることが明らかになった。