Changes in the dynamics of the cardiac troponin C molecule explain the effects of Ca²⁺-sensitizing mutations.

ABSTRACT: Cardiac troponin C (cTnC) is the regulatory protein that initiates cardiac contraction in response to Ca²⁺ TnC binding Ca²⁺ initiates a cascade of protein-protein interactions that begins with the opening of the N-terminal domain of cTnC, followed by cTnC binding the troponin I switch peptide (TnI_SW). We have evaluated, through isothermal titration calorimetry and molecular-dynamics simulation, the effect of several clinically relevant mutations (A8V, L29Q, A31S, L48Q, Q50R, and C84Y) on the Ca²⁺ affinity, structural dynamics, and calculated interaction strengths between cTnC and each of Ca²⁺ and TnI_SW Surprisingly the Ca²⁺ affinity measured by isothermal titration calorimetry was only significantly affected by ha

SUBMITTER: Stevens CM 

PROVIDER: S-EPMC5512083 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature