Presentation Effects of E244D mutation of cardiac troponin T on the structure of thin filaments by small-angle x-ray scattering

松尾, 龍人  ,  松尾龍人  ,  河野, 史明  ,  藤原, 悟

In order to investigate the effects of a cardiomyopathy-causing mutation E244D of troponin (Tn) T on the structure of thin filaments, small-angle x-ray scattering measurements were carried out on bovine cardiac thin filaments, in which the endogenous Tn was exchanged with human cardiac Tn containing the wild-type (WT) or E244D mutant (MT) of TnT, in the –Ca2+ and +Ca2+ states. Analysis by model calculation shows that while there are no structural differences between the WT and MT in the –Ca2+ state, tropomyosin (Tm) of the MT moves closer to the fiber axis than that of the WT in the +Ca2+ state. Since Tm directly controls myosin binding, this change would modulate the force production process, leading to functional aberration reported for the E244D mutation.

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