Hypertrophic cardiomyopathy-linked mutation D145E drastically alters calcium binding by the C-domain of cardiac troponin C.

ABSTRACT: The role of the C-domain sites of cardiac troponin C in the modulation of the calcium signal remains unclear. In this study, we investigated the effects of hypertrophic cardiomyopathy-linked mutations A8V, E134D, and D145E in cardiac troponin C on the properties of the C-domain sites. The A8V mutation had essentially no effect on the calcium or magnesium binding properties of the C-domain sites, while the mutation E134D moderately decreased calcium and magnesium binding affinities. On the other hand, the D145E mutation affected cooperative interactions between sites III and IV, significantly reducing the calcium binding affinity of both sites. Binding of the anchoring region of cardiac troponin I (corresponding to residues 34-71) to cardiac troponin C with the D145E mutation was not able t

SUBMITTER: Swindle N 

PROVIDER: S-EPMC2883812 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature