Structural biology studies of autophagy-related protein Atg9

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: Matoba Kazuaki 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (60613792)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: オートファジー / クライオ電子顕微鏡

Outline of Final Research Achievements

During this study, we showed that the recombinant Atg9 had lipid scrambling activity in vitro. Atg9 structure was then determined by single particle analysis using cryo-EM (3.0Å resolution). Based on the structure, mutants were prepared, and mutants with reduced lipid scrambling activity were found. These mutants were not able to elongate isolation membranes in yeast. This suggests that the lipid scrambling activity of Atg9 is necessary for the normal progression of autophagy.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

オートファジーが機能する上で必須のタンパク質であるAtg9の機能と立体構造を明らかにし、オートファジーの特徴である隔離膜がどのように伸びるのか、膜伸展モデルを提唱することができた。これらの作動原理は学術的にインパクトがあるだけでなく、Atg9の構造をもとにしたオートファジー制御剤の開発に貢献できる。