Investigation for the mechanism of the gastric proton pump that generates the steepest cation gradient

2017 Fiscal Year Final Research Report

• Project/Area Number: 26711005
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Nagoya University
• Principal Investigator: Abe Kazuhiro 名古屋大学, 細胞生理学研究センター, 准教授 (60596188)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: P型ATPase / 膜タンパク質 / 電子顕微鏡 / 膜輸送体 / 胃プロトンポンプ

Outline of Final Research Achievements

Gastric proton pump is a membrane protein responsible for the gastric acid secretion, therefore it is a molecular target for the anti-ulcer drug. In this research, we attempt to determine its structure by both electron and X-ray crystallography, and establish a large-scale expression system using mammalian cells for the functional analysis and X-ray crystallography.
We proposed the binding model of acid suppressants to the gastric proton pump, by using electron crystallographic structure analyzed at 6.5 A resolution, which is conformed by the mutagenesis and derivatives of acid suppressants.
Furthermore, we successfully established the mammalian cell expression system, which allow us to generate 3D crystals for X-ray. Determined structure reveals the mechanism of proton extrusion to the highly acidic solution of the stomach.

Free Research Field

膜輸送体