Calsequestrin interacts directly with the cardiac ryanodine receptor luminal domain.

Cardiac muscle contraction requires sarcoplasmic reticulum (SR) Ca release mediated by the quaternary complex comprising the ryanodine receptor 2 (RyR2), calsequestrin 2 (CSQ2), junctin (encoded by ASPH) and triadin. Here, we demonstrate that a direct interaction exists between RyR2 and CSQ2. Topologically, CSQ2 binding occurs at the first luminal loop of RyR2.