title: Three-dimensional reconstruction of ryanodine receptors.
abstract: Nearly all available information on the three-dimensional structure of the ryanodine receptor (RyR) class of intracellular calcium release channels has come from electron microscopy. This review focuses on results that have been obtained by cryo-electron microscopy of purified, detergent-solubilized receptors in combination with single-particle image processing. This approach has led to the most detailed 3D models of RyRs, which are currently at resolutions of 20-30  . All three of the known genetic isoforms show essentially identical architectures at this resolution: a large, 4-fold symmetric, cytoplasmic assembly that accounts for greater than 80% of the receptor's mass and is composed of at least 10 discrete, loosely packed domains, and a transmembrane region whose dimensions lead us to conclude that very little of RyR's protein mass is present on the lumenal side of the sarco/endoplasmic reticulum. Three-dimensional reconstructions determined for RyRs that have been exposed to conditions that promote either open or closed states show subtle differences, some of which are located in the cytoplasmic assembly, at sites more distant than 100   from the ion channel in the transmembrane region. Several of the ligands (FK506-binding protein, calmodulin, dihydropyridine receptor) that interact in vivo with the skeletal RyR have been, or are in the process of being, mapped to various locations on the cytoplasmic assembly.
authors.affiliation: Biggs Laboratory, Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA. tcw02@wcnotes.wadsworth.org
authors.forename: Terence
authors.initials: T
authors.lastname: Wagenknecht
authors.forename: Montserrat
authors.initials: M
authors.lastname: Samsó
mesh_terms: D000818:Animals; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D011487:Protein Conformation; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel