Calcium (Ca2+) is the primary messenger in muscle excitation-contraction, the process by which cells rapidly depolarize, release stored Ca2+ into the cytosol, thereby promoting myofilament contraction.  Calcium entry is regulated by trans-membrane ion transporters and proteins involved in signaling and myofilament contraction. Molecular-scale factors, including sequence, electrostatics and post-translational modification are determinants of Ca2+ handling efficacy. In this study we examine electrostatics and conformational fluctuations that modulate Ca2+ binding to the myofilament protein Troponin C (TnC)and the sarcolemmal reticulum Ca2+ ATPase (SERCA). Using molecular dynamics and Brownian dynamics, we have quantified diffusion-limited Ca2+ association rates (kon) for predominant conformational states of these proteins. Invoking a Markov model for conformations in steady-state, each with an intrinsic binding, we have quantified gating effects that modulate observed Ca2+ kon. These studies provide insight into dynamic, molecular-scale factors that  ultimately regulate Ca2+ dynamics in EC coupling.

Stochastic gating regulates calcium association rates in Troponin C and SERCA

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.