Molecular mechanisms of AAA proteins revealed by biochemical analyses and high-speed atomic force microscopic observations

2014 Fiscal Year Final Research Report

• Project/Area Number: 24370056
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kumamoto University
• Principal Investigator: OGURA Teru 熊本大学, 発生医学研究所, 教授 (00158825)
• Co-Investigator(Renkei-kenkyūsha): OKUNO Takashi 山形大学, 理学部, 准教授 (80411031) ; YAMANAKA Kunitoshi 熊本大学, 発生医学研究所, 准教授 (90212290) ; ESAKI Masatoshi 熊本大学, 発生医学研究所, 助教 (70437911)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: AAAタンパク質 / 分子シャペロン / プロテアソーム / p97/VCP/CDC-48/Cdc48 / Katanin / 高速原子間力顕微鏡 / ミトコンドリア / 微小管

Outline of Final Research Achievements

AAA family chaperones/proteases form a hexameric ring structure. ATP-dependent rotation of the AAA chaperone p97 was analyzed by high-speed AFM, and a novel model for the p97 action against substrate has been proposed. It has been found that VCP, a human p97 homolog, binds to amyloid fibrils of TDP-43. UFD-3 is an adapter of CDC-48, a C. elegans p97 homolog, and has been revealed to regulate polyglutamine aggregate formation. Abnormal mitochondrial morphology caused by a mutation of Cdc48, a yeast p97 homolog, was precisely analyzed by advanced microscopic techniques. Dynamics of the 26S proteasome and its complex with a substrate were analyzed by high-speed AFM. Microtubule severing by katanin was analyzed, and a novel model for the mechanism of katanin has been proposed. Functional importance of mitochondrial Bcs1 was revealed.

Free Research Field

生物学