Structure-based mechanism of RyR channel operation by calcium and magnesium ions
Fig 9
The COI model of RyR channel operation.
(A) Transitions between the closed, open, and inactivated macrostates of ligand-free RyR. Equilibrium constants of transitions between the respective macrostates are indicated. (B) The ligand-binding transitions of a monomer in the closed macrostate. (C) The ligand-binding transitions of a monomer in the open macrostate. (D) The ligand-binding transitions of a monomer in the inactivated macrostate. (B – D) Gray shapes represent RyR monomers in the respective macrostates as depicted in A. Equilibrium constants of transitions between the respective states are indicated. Lines and arrows represent the allosteric interaction pathways. Dashed lines - no allosteric regulation. Blunt arrow (Ͱ) - negative allosteric interaction. The pointed arrows (←) - positive allosteric interaction. Round groove – the activation site. Pointed groove – the inhibition site. Blue square – the interaction site of the activation and the intra-monomeric inhibition pathways (ATP-binding site). Red circles – Ca2+; pink circles – Mg2+; green diamonds – M2+ (Ca2+ or Mg2+). Brown shapes labeled G - the channel pore with the gate in the closed, open, or inactivated state. The grey triangle represents the S23 loop of a neighboring monomer.