Contributions of electron microscopy and single-particle techniques to the determination of the ryanodine receptor three-dimensional structure.
The ryanodine receptor is the main intracellular calcium release channel from the sarcoplasmic reticulum in striated muscle. It is the largest ion channel known, composed of four identical major subunits of 565 kDa and four smaller 12-kDa subunits, identified as FK-506 binding protein. The successful isolation of the ryanodine receptor together with the development of cryoelectron microscopy and single-particle image processing techniques have enabled major progress to be made in the determination of the receptor's structure over the past decade. Three-dimensional reconstruction shows the receptor to be composed of two main parts, a large square shaped cytoplasmic assembly and a smaller transmembrane assembly. The cytoplasmic assembly has an unusual architecture in which about 10 domain-like structures are interconnected in a loosely packed manner. Subsequent studies have started to reveal conformational changes associated with channel gating and the localization of binding sites for some proteins with which the receptor interacts (calmodulin, and FK-506 binding protein). It is becoming clear that long-range induced conformational changes must be involved in the mechanisms of modulation of the receptor's gating properties.
Samsó
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Division of Molecular Medicine, Wadsworth Center, Albany, New York 12201-0509, USA.
Wagenknecht
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T
D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D002155:Calsequestrin / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004095:Dihydropyridines / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008854:Microscopy, Electron; D008958:Models, Molecular; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism / Q000648:ultrastructure; D016559:Tacrolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins
D002147:Calmodulin; D002155:Calsequestrin; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004095:Dihydropyridines; D006360:Heat-Shock Proteins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C070048:triadin; C038806:1,4-dihydropyridine; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus