Dynamics measurements of a cardiomyopathy-causing mutant of troponin

2017 Fiscal Year Final Research Report

• Project/Area Number: 26750367
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: National Institutes for Quantum and Radiological Science and Technology (2016-2017); Japan Atomic Energy Agency (2014-2015)
• Principal Investigator: MATSUO Tatsuhito 国立研究開発法人量子科学技術研究開発機構, 高崎量子応用研究所 東海量子ビーム応用研究センター, 主任研究員(定常) (60623907)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: トロポニン / 心筋症 / ダイナミクス / 中性子散乱 / タンパク質

Outline of Final Research Achievements

In this study, effects of a cardiomyopathy-causing mutation on the picosecond dynamics of human cardiac troponin core domain (Tn-CD, which consists of TnC, TnI, and TnT2) were investigated using quasielastic neutron scattering (QENS). QENS measuremnts were conducted on solution samples of Tn-CD containing either the wild-type (WT) or the K247R mutant (MT) of TnT2. It was found that in the -Ca state, the mutation decreases the residence time of local atomic motions, suggesting that the hydrogen bond network within the Tn-CD is disrupted. Upon Ca-binding, while the amplitudes of atomic motions in the WT tended to decrease, those of the MT was found to increase, indicating that the atoms of the MT can explore larger conformational space than those of the WT. Since the functional aberration caused by the K247R mutation is observed only in the +Ca state, these data suggest that the larger amplitudes of the MT are related to the pathogensis of hypertrophic cardiomyopathy.

Free Research Field

生物物理学, 中性子散乱, X線散乱