| Project/Area Number |
17H07031
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Nara Medical University |
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Principal Investigator |
Mori Eiichiro 奈良県立医科大学, 医学部, 准教授 (70803659)
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| Research Collaborator |
Kato Masato University of Texas Southwestern Medical Center, Department of Biochemistry, Associate Professor
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| 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 / cross-betaポリマー / アミロイド様線維 / 液-液相分離 / 化学的Foot-print法 / cross-beta polymer / low complexityドメイン / 化学的Footprint法 |
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| 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.
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| 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。
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