The N-Terminal Region of the Ryanodine Receptor Affects Channel Activation.

ABSTRACT: Mutations in the cardiac ryanodine receptor (RyR2), the ion channel responsible for release of calcium ions from intracellular stores into cytoplasm, are the cause of several inherited cardiac arrhythmias. At the molecular level, disease symptoms can be mimicked by domain peptides from mutation-prone regions of RyR2 that bind to RyR2 and activate it. Here we show that the domain peptide DP_cpvtN2, corresponding to the central helix of the N-terminal region of RyR2, activates the RyR2 channel. Structural modeling of interaction between DP_cpvtN2 and the N-terminal region of RyR2 in the closed and open conformation provided three plausible structures of the complex. Only one of them could explain the dependence of RyR2 activity on concentration of DP_cpvtN2. The

SUBMITTER: Faltinova A 

PROVIDER: S-EPMC5492033 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature