The skeletal muscle Ca(2+) release channel has an oxidoreductase-like domain

We used a combination of bioinformatics, electron cryomicroscopy, and biochemical techniques to identify an oxidoreductase-like domain in the skeletal muscle Ca(2+) release channel protein (RyR1). The initial prediction was derived from sequence-based fold recognition for the N-terminal region (41–420) of RyR1. The putative domain was computationally localized to the clamp domain in the cytoplasmic region of a 22Å structure of RyR1. This localization was subsequently confirmed by difference imaging with a sequence specific antibody. Consistent with the prediction of an oxidoreductase domain, RyR1 binds [(3)H]NAD(+), supporting a model in which RyR1 has a oxidoreductase-like domain that could function as a type of redox sensor.