| Project/Area Number |
09670702
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | University of Tokyo |
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Principal Investigator |
SUGIURA Seiryo University of Tokyo, Dept. of cardiovascular medicine, assistant professor, 医学部・附属病院, 助手 (10272551)
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| Co-Investigator(Kenkyū-buntansha) |
AOYAGI Teruhiko University of Tokyo, Dept. of cardiovascular medicine, assistant professor, 医学部・附属病院, 助手 (10251240)
MOMOMURA Shin-ichi University of Tokyo, Dept. of cardiovascular medicine, assistant professor, 医学部・附属病院, 助手 (10190985)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | myosin / molecular biology / in vitro motiliy assay / optical tweezer / インビトロ アッセイ |
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| Research Abstract |
To screen recombinant myosin which has high contractile performance. We studied the mechanical as well as biochemical characteristics of various myosin species obtained from animal model and genetically designed and expressed in cell culture. We constructed an in vitro motility assay system coupled with an optical tweezer with which we could measure the force generated by a single myosin molecule and actin filament (unitary force). We compared the unitary force generated by two cardiac myosin isoforms, V1 and V3 to find the force of two isoforms differs in duration but not in amplitude. We considered that this difference in duration of force causes the distinct energetic characteristics of these isoforms. We also evaluated the properties of mutant myosin implicated in human familial hypertrophic cardiomyopathy. We constructed recombinant myosin molecules whose mutations were located in ATPase domain, actin binding domain, proximity of reactive cysteine, and interface of light chain. We found a discrepancy between ATPase and force generating ability in these mutations. Poor prognosis of patients with these mutations suggested the significant role of these malfunctioning myosin in the pathogenesis of hypertrophic cardiomyopathy. It also showed that functional improvement of myosin by an alteration of molecular structure could be a potential treatment of heart disease.
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