Structural study of LC domains of intermediate filaments

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H07031
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Nara Medical University
• Principal Investigator: Mori Eiichiro 奈良県立医科大学, 医学部, 准教授 (70803659)
• Research Collaborator: Kato Masato University of Texas Southwestern Medical Center, Department of Biochemistry, Associate Professor
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: LCドメイン / 中間径フィラメント / Desmin / Headドメイン / cross-βポリマー / 固体NMR / Intein反応

Outline of Final Research Achievements

Protein segments of low sequence complexity/intrinsic disorder (LC domains) are now recognized to play roles in the basis of the membrane-less organelles through cross-β polymerization. Desmin myopathy is a disease associated with mutations in desmin gene, presenting skeletal myopathy combined with cardiomyopathy. Desmin is a type of intermediate filaments, one of the cytoskeletal proteins. All intermediate filaments contain LC domains on both the amino- and carboxyl-terminal sides of the central coiled coil domain. The amino-terminal LC sequences of intermediate filament proteins are referred to as head domains, the carboxyl-terminal LC sequences are termed tail domains. Introducing patient-derived mutations accelerates cross-β polymerization. We detected signals by solid-state NMR, and with intein technology we successfully obtained the NMR signal out of segmentally labeled intermediate filaments.

Free Research Field

生化学、蛋白質科学、細胞生物学

Academic Significance and Societal Importance of the Research Achievements

今後さらに、中間径フィラメントのHeadドメインによって形成されるcross-βポリマーの構造を明らかにすることで、中間径フィラメントによる細胞形態のより詳細な知見につながる。中間径フィラメントのHeadドメインのcross-βポリマー形成に着目した本研究は、他に類を見ない独創的な研究であり、本研究によってもたらされる成果は、細胞の形態のさらなる理解につながり、様々な生命科学領域に大きな影響を与えるであろう。これらの研究成果から、ミオパチーの疾患治療法の開発につながることが期待される。