Cryo-Em Studies of Phosphomimetic and Phospho-Null Triple Mutants of Cardiac Ryanodine Receptor (RyR2)

Abstract

The activity of cardiac ryanodine receptor type 2 (RyR2), a key player in cardiac contractility, is modulated by various post-translational modifications including phosphorylation at three key residues: S2808, S2814, and S2030. Out of these, two residues (S2808 and S2814) lie in a highly flexible loop of the phosphorylation (P2) domain which has remained unresolved in full-length RyR and in crystal structures of the P2 domain alone. This domain faces the inter-subunit interface near the corner of the square prism-shaped cytoplasmic assembly.