Ryanodine receptor assembly: A novel systems biology approach to 3D mapping

Ryanodine receptors (RyRs) are intracellular Ca2+ release channels (CRCs) that play a pivotal role in cellular Ca2+ signaling. In striated muscles, RyR-mediated Ca2+ release from the sarcoplasmic reticulum (SR) induces elevation of cytosolic Ca2+ concentration and subsequent muscle contraction. Evidence from various sources suggests that RyRs in homo-tetrameric conformation form a large conductance Ca2+ permeable channel in the central pore and large cytoplasmic domains. RyRs form a large assembly with various cytosolic and luminal proteins. A number of papers have been published concerning the functions of RyRs and the regulation of the associated proteins, but the three dimensional (3D) structure of the assembly has not been addressed in detail. In this paper, we have attempted to establish a 3D-map for the assembly of RyRs by considering published cryo-EM data, available X-ray crystallographic information and molecular modeling methods.