HRC (histidine-rich Ca2+ binding protein) resides in the lumen of sarcoplasmic reticulum as a multimer

HRC (histidine-rich Ca2+ binding protein) has been identified from skeletal and cardiac muscle and shown to bind Ca2+ with low affinity and high capac ity that is reminiscent of calsequestrin. The physiological role of HRC is largely unknown. In this study, we show that HRC exists as a multimeric com plex (probably larger than a pentamer) under physiological conditions. At h igher Ca2+ concentrations, the complex appeared to dissociate into dimers o r trimers that form a more relaxed structure. This is in striking contrast to the characteristics of calsequestrin, An earlier immunoelectron microsco pic study showed that HRC resides in the lumen of the sarcoplasmic reticulu m (SR), but this conclusion has been challenged by other data. By tryptic d igestion and biotinylation of SR vesicles, we provide compelling evidence s howing that HRC is indeed present in the lumen of the SR. (C) 1999 Academic Press.