Cysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR).

ABSTRACT: The most common cardiac pathologies, such as myocardial infarction and heart failure, are associated with oxidative stress. Oxidation of the cardiac ryanodine receptor (RyR2) Ca²⁺ channel causes spontaneous oscillations of intracellular Ca²⁺, resulting in contractile dysfunction and arrhythmias. RyR2 oxidation promotes the formation of disulfide bonds between two cysteines on neighboring RyR2 subunits, known as intersubunit cross-linking. However, the large number of cysteines in RyR2 has been a major hurdle in identifying the specific cysteines involved in this pathology-linked post-translational modification of the channel. Through mutagenesis of human RyR2 and in-cell Ca²⁺ imaging, we identify that only two cysteines (out of 89) in each RyR2 subunit are

SUBMITTER: Nikolaienko R 

PROVIDER: S-EPMC10372021 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature