The cardiac-specific N-terminal region of troponin I positions the regulatory domain of troponin C

Protein-protein interactions typically involve some degree of induced fit, producing complementary surfaces that account for high affinity and specificity. However, there are increasingly more examples of intrinsically disordered regions (IDRs) that exert important biologic effects despite never attaining a rigid structure. Here we show how a particularly disordered region of cardiac troponin I impacts the overall global conformation and function of its binding partner, cardiac troponin C. This newly described role for an IDR is accomplished through electrostatic interactions, which are particularly suited to IDRs. The regulation of electrostatic interactions in IDRs through phosphorylation is an emerging concept in cellular signaling, and troponin I is now another important example, one known by cardiac physiologists for 40 y.