Structures of the troponin core domain containing the cardiomyopathy-causing mutants studied by small-angle X-ray scattering

X線小角散乱による心筋症原因変異体を含むトロポニンコア領域の構造研究

松尾 龍人; 武田 壮一*; 小田 俊郎*; 藤原 悟

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

Troponin (Tn), consisting of three subunits, TnC, TnI, and TnT, is a protein that plays a major role in regulation of muscle contraction. Various mutations of Tn cause familial hypertrophic cardiomyopathy. Here we focus on the mutations E244D and K247R of TnT, which induce an increase in the maximum tension of cardiac muscle without changes in Ca-sensitivity, and carried out small-angle X-ray scattering experiments on the Tn core domain containing the wild type subunits and those containing the mutant TnT in the absence and presence of Ca. Changes in the overall shape induced by the mutations were detected for the first time by the changes in the radius of gyration and the maximum dimension between the wild type and the mutants. Analysis by model calculations shows that TnC adopts a dumbbell structure regardless of the mutations, and that the mutations change the distributions of the conformational ensembles so that the flexible N- and C-terminal regions of TnT become close to the center of the whole molecule.