CONTRIBUTIONS OF ELECTRON-MICROSCOPY AND SINGLE-PARTICLE TECHNIQUES TO THE DETERMINATION OF THE RYANODINE RECEPTOR 3-DIMENSIONAL STRUCTURE

The ryanodine receptor is the main intracellular calcium release chann el from the sarcoplasmic reticulum in striated muscle. It is the large st ion channel known, composed of four identical major subunits of 565 kDa and four smaller 12-kDa subunits, identified as FK-506 binding pr otein. The successful isolation of the ryanodine receptor together wit h the development of cryoelectron microscopy and single-particle image processing techniques have enabled major progress to be made in the d etermination of the receptor's structure over the past decade. Three-d imensional reconstruction shows the receptor to be composed of two mai n parts, a large square shaped cytoplasmic assembly and a smaller tran smembrane assembly. The cytoplasmic assembly has an unusual architectu re in which about 10 domain-like structures are interconnected in a lo osely packed manner. Subsequent studies have started to reveal conform ational changes associated with channel gating and the localization of binding sites for some proteins with which the receptor interacts (ca lmodulin, and FK-506 binding protein). It is becoming clear that long- range induced conformational changes must be involved in the mechanism s of modulation of the receptor's gating properties. (C) 1998 Academic Press.