title: Ryanodine receptor calcium release channels: lessons from structure-function studies.
abstract: Ryanodine receptors (RyRs) are the largest known ion channels. They are Ca(2+) release channels found primarily on the sarcoplasmic reticulum of myocytes. Several hundred mutations in RyRs are associated with skeletal or cardiomyocyte disease in humans. Many of these mutations can now be mapped onto the high resolution structures of individual RyR domains and on full-length tetrameric cryo-electron microscopy structures. A closely related Ca(2+) release channel, the inositol 1,4,5-trisphospate receptor (IP3 R), shows a conserved structural architecture at the N-terminus, suggesting that both channels evolved from an ancestral unicellular RyR/IP3 R. The functional insights provided by recent structural studies for both channels will aid in the development of rationale treatments for a myriad of Ca(2+)-signaled malignancies.
authors: Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Canada.
authors: Fernando J
authors: FJ
authors: Amador
authors: Peter B
authors: PB
authors: Stathopulos
authors: Masahiro
authors: M
authors: Enomoto
authors: Mitsuhiko
authors: M
authors: Ikura
mesh_terms: D000818:Animals; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D019837:Ryanodine Receptor Calcium Release Channel
keywords: X-ray crystallography; cryo-electron microscopy; excitation-contraction coupling; inositol 1,4,5-trisphosphate receptor; malignant hyperthermia; nuclear magnetic resonance spectroscopy; ryanodine receptor