Structural study on the role of post-translational lipid modifications of the small G protein Ras

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293065
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: KATAOKA TOHRU 神戸大学, 大学院医学研究科, 教授 (40144472)
• Co-Investigator(Kenkyū-buntansha): 島 扶美 神戸大学, 医学(系)研究科(研究院), 教授 (60335445) ; 枝松 裕紀 神戸大学, 医学(系)研究科(研究院), 助教 (70335438) ; 松本 篤幸 神戸大学, 医学(系)研究科(研究院), 助教 (00753906)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: シグナル伝達 / 蛋白質 / 癌 / 脂質 / 高分子構造・物性

Outline of Final Research Achievements

We succeeded in large scale preparation and purification of the post-translationally lipid-modified form of H-Ras protein and various intermediates of the modification by utilizing the protein-ligation reaction catalyzed by Sortase A. Structural analyses of the GTP-bound form of post-translationally-modified H-Ras using nuclear magnetic resonance spectroscopy and X-ray crystallography revealed that the modified C terminus established an intramolecular interaction with the N-terminal catalytic domain of H-Ras and positioned the post-translationally-attached farnesyl moiety at the proximity of the activator region, thereby forming a new binding interface for a Ras effector protein, c-Raf-1.

Free Research Field

細胞内情報伝達