Structural and functional consequences of cardiac troponin C L57Q and I61Q Ca2+-desensitizing variants

► Study of L57Q and I61Q cTnC using solution and in silico techniques is presented. ► Solution studies indicate both variants decrease the Ca2+ binding affinity to cTnC. ► Both variants reduced cTnI affinity to cTnC in Ca2+ saturated states. ► MD simulation shows disruption between helices B/C by both cTnC variants. ► cTnC (I61Q) formed hydrogen bonds with the residues on the Ca2+ binding loop.