Identification of an amino-terminus determinant critical for ryanodine receptor/Ca2+ release channel function.

ABSTRACT:

Aims

The cardiac ryanodine receptor (RyR2), which mediates intracellular Ca2+ release to trigger cardiomyocyte contraction, participates in development of acquired and inherited arrhythmogenic cardiac disease. This study was undertaken to characterize the network of inter- and intra-subunit interactions regulating the activity of the RyR2 homotetramer.

Methods and results

We use mutational investigations combined with biochemical assays to identify the peptide sequence bridging the β8 with β9 strand as the primary determinant mediating RyR2 N-terminus self-association. The negatively charged side chains of two aspartate residues (D179 and D180) within the β8-β9 loop are crucial for the N-terminal inter-subunit interaction. We also show that the RyR2 N-terminus domain interac

SUBMITTER: Seidel M 

PROVIDER: S-EPMC7898959 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature