Novel techniques to investigate function-related dynamics of membrane proteins

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21473
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Kofuku Yutaka 東京大学, 大学院薬学系研究科(薬学部), 助教 (80737940)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 核磁気共鳴法 / 膜タンパク質

Outline of Final Research Achievements

Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to investigate the function-related dynamics of membrane proteins. However, NMR analyses of membrane proteins are still challenging, because methods for observations of NMR signals of large proteins expressed in a mammalian expression system are limited. Here, we developed a method to incorporate 13C-labeled methyl groups in highly deuterated proteins expressed in mammalian expression systems. The developed method enabled the NMR ananlyses of pharmaceutically important membrane proteins with high sensitivities.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

本手法を、様々な創薬標的膜タンパク質に適用することで、NMR法を用いた動的構造解析が飛躍的に進展し、膜タンパク質の動作する様を精緻に描写することが可能になる。従来の創薬研究では、静的な高分解能構造にもとづき、標的タンパク質に高い親和性で結合する化合物の創製が主流であった。一方、NMR法を用いた動的構造解析が進展すれば、動的構造にもとづき、望ましい活性を有する化合物を戦略的に設計するなど、新たな創薬戦略が期待できる。