Amide hydrogens reveal a temperature-dependent structural transition that enhances site-II Ca²⁺-binding affinity in a C-domain mutant of cardiac troponin C.

ABSTRACT: The hypertrophic cardiomyopathy-associated mutant D145E, in cardiac troponin C (cTnC) C-domain, causes generalised instability at multiple sites in the isolated protein. As a result, structure and function of the mutant are more susceptible to higher temperatures. Above 25 °C there are large, progressive increases in N-domain Ca²⁺-binding affinity for D145E but only small changes for the wild-type protein. NMR-derived backbone amide temperature coefficients for many residues show a sharp transition above 30-40 °C, indicating a temperature-dependent conformational change that is most prominent around the mutated EF-hand IV, as well as throughout the C-domain. Smaller, isolated changes occur in the N-domain. Cardiac skinned fibres reconstituted with D145E are more sensitive to Ca<

SUBMITTER: Veltri T 

PROVIDER: S-EPMC5429600 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature