Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study.

ABSTRACT: Mutations in cardiac troponin C (D75Y, E59D, and G159D), a key regulatory protein of myofilament contraction, have been associated with dilated cardiomyopathy (DCM). Despite reports of altered myofilament function in these mutants, the underlying molecular alterations caused by these mutations remain elusive. Here we investigate in silico the intramolecular mechanisms by which these mutations affect myofilament contraction. On the basis of the location of cardiac troponin C (cTnC) mutations, we tested the hypothesis that intramolecular effects can explain the altered myofilament calcium sensitivity of force development for D75Y and E59D cTnC, whereas altered cardiac troponin C-troponin I (cTnC-cTnI) interaction contributes to the reported contractile effects of the G159D mutation. We emplo

SUBMITTER: Dewan S 

PROVIDER: S-EPMC5001916 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature