Structural basis for the ion channel anchoring of ankyrinG

2014 Fiscal Year Final Research Report

• Project/Area Number: 24689012
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: General physiology
• Research Institution: Osaka University
• Principal Investigator: FUJIWARA YUICHIRO 大阪大学, 医学(系)研究科(研究院), 准教授 (20532980)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 興奮収縮連関 / 跳躍伝導 / イオンチャネル / 構造機能連関 / パルミトイル化

Outline of Final Research Achievements

Ankyrin-G (AnkG) configures the membrane-excitation platform by clustering various ion channels in neurons and cardiomyocytes. AnkG itself localizes to the specific areas on the plasma membrane via the s-palmitoylation of Cys. However, the structural mechanism how AnkG anchors to the membrane is not understood. In this study, we solved the crystal structures of the s-palmitoylation domain of AnkG in reduced and oxidized forms of the Cys, and performed the long-term molecular dynamics simulation of the membrane association. Here we report that the s-palmitoylation facilitated the membrane anchoring of AnkG, defining a stable binding interface to the plasma membrane. AnkG without s-palmitoylation was apparently in contact with the membrane but did not have a unique binding interface. These suggest that AnkG is ready to accept the Cys modification in the juxtamembrane region, and, once it happens, constitutes the rigid structural base of the membrane-excitation platform.

Free Research Field

生理学