Dynamics-Driven Allostery Underlies Ca²⁺-Mediated Release of SERCA Inhibition by Phospholamban.

ABSTRACT: Sarcoplasmic reticulum (SR) Ca²⁺-ATPase (SERCA) and phospholamban (PLB) are essential for intracellular Ca²⁺ transport in myocytes. Ca²⁺-dependent activation of SERCA-PLB provides a control function that regulates cytosolic and SR Ca²⁺ levels. Although experimental and computational studies alone have led to a greater insight into SERCA-PLB regulation, the structural mechanisms for Ca²⁺ binding reversing inhibition of the complex remain poorly understood. Therefore, we have performed atomistic simulations totaling 32.7 μs and cell-based intramolecular fluorescence resonance energy transfer (FRET) experiments to determine structural changes of PLB-bound SERCA in response to binding of a single Ca²⁺ ion. Complementary MD simul

SUBMITTER: Raguimova ON 

PROVIDER: S-EPMC7677127 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature