Molecular basis of the ULK complex that regulates mammalian autophagy initiation.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14641
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Toho University
• Principal Investigator: SUZUKI Hironori 東邦大学, 薬学部, 講師 (20625694)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: オートファジー / X線結晶構造解析 / 分子間相互作用

Outline of Final Research Achievements

Many proteins involved in autophagy are widely conserved in eukaryotes from budding yeast to humans. However, some of the proteins are unique to higher eukaryotes such as humans. Analysis of the structure and function of these proteins are essential to understand autophagy in higher eukaryotes.
In this study, I focused on FIP200, which is one of the factors unique to higher eukaryotes. Moreover, I analyzed the interaction of FIP200 with each factor of ULK complex, ULK1, Atg13 and Atg101, involved in autophagy initiation in higher eukaryotes. I found that Atg101 interacted only with Atg13, while the other three interacted with each other to form ULK complex. The mode of interaction of the three proteins in higher eukaryotes had some similarities with budding yeast homologues, while some specificity to higher eukaryotes.

Free Research Field

構造生物化学

Academic Significance and Societal Importance of the Research Achievements

生命科学研究は生体構成の単純なモデル生物を利用して，その作動原理や機能を解明することが多いが，一方でそれは必ずしもヒトなどの高等生物にそのまま当てはめることができない。オートファジーはモデル生物として出芽酵母を用いてその基本的な作動原理の多くが解明されてきたが，本研究はヒトのタンパク質を用いて実施した研究であり，得られた知見も出芽酵母とは似て非なる部分もあった。そのため，ヒトなどの高等生物のオートファジーの理解や，オートファジーが関わる疾患の解明やその治療薬開発の一助になることが期待される。