Molecular Basis of S100A1 Activation and Target Regulation Within Physiological Cytosolic Ca²⁺ Levels.

ABSTRACT: The S100A1 protein regulates cardiomyocyte function through its binding of calcium (Ca²⁺) and target proteins, including titin, SERCA, and RyR. S100A1 presents two Ca²⁺ binding domains, a high-affinity canonical EF-hand (cEF) and a low-affinity pseudo EF-hand (pEF), that control S100A1 activation. For wild-type S100A1, both EF hands must be bound by Ca²⁺ to form the open state necessary for target peptide binding, which requires unphysiological high sub-millimolar Ca²⁺ levels. However, there is evidence that post-translational modifications at Cys85 may facilitate the formation of the open state at sub-saturating Ca²⁺ concentrations. Hence, post-translational modifications of S100A1 could potentially increase the Ca²⁺-sensit

SUBMITTER: Sun B 

PROVIDER: S-EPMC7324869 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature