Dynamics of cardiomyopathy-causing mutant of troponin observed by neutron scattering

Matsuo, Tatsuhito; Natali, F.*; Zaccai, G.*; Fujiwara, Satoru

Troponin is a protein that regulates the muscle contraction depending on the intracellular Ca2+ concentration. K247R mutation of TnT is known to cause the hypertrophic cardiomyopathy. In this work, neutron scattering was used to detect possible changes in dynamics of troponin caused by mutation. Elastic incoherent neutron scattering experiments were carried out on solution samples of the wild type, and K247R mutant at the IN13 spectrometer at the Institut Laue-Langevin, at temperatures between 280 K and 292 K with an interval of 3 K. From the measured scattering data, force constants (k), which reflect the resilience of the protein, were calculated. The k values for the wild type and K247R mutant were 0.077 (0.035) N/m and 0.046 (0.026) N/m (mean(s.d.)), respectively. This suggests that the disease-causing mutant is more flexible than the wild type. The large flexibility might modulate Ca2+ signal transmission mechanism, leading to the functional aberration.