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Report No.

Structural changes of troponin by cardiomyopathy-causing mutations

Fujiwara, Satoru; Matsuo, Tatsuhito; Matsumoto, Fumiko; Oda, Toshiro*; Takeda, Soichi*

Various mutations in the regulatory proteins of muscle contraction, troponin (Tn), consisting of three subunits, TnC, TnI, and TnT, have been reported to cause familial hypertrophic cardiomyopathy. To elucidate the molecular mechanism of pathogenesis of these mutations, we focus on the mutations in the coiled-coil region of TnT, E244D and K247R, and performed small-angle X-ray scattering (SAXS) experiments on the solutions of Tn containing wild-type TnT, and those containing mutant TnT. It was shown that the structural changes of Tn are induced by these mutations. Analysis by molecular modeling suggested that these changes arise from the changes in the conformational fluctuations rather than distinct structural changes.



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