title: Revisiting channel allostery: a coherent mechanism in IP₃ and ryanodine receptors.
abstract: The inositol 1,4,5-trisphosphate (IP₃) receptor is an IP₃-gated calcium ion (Ca²⁺) channel that mediates intracellular IP₃-Ca²⁺ signaling. A fundamental question--how IP₃ gates the Ca²⁺ channel within the IP₃ receptor--remains unanswered. A new crystal structure of the N-terminal region of the IP₃ receptor reveals allosteric changes by ligand binding and its similarity to the corresponding region of ryanodine receptor. Docking of the crystal structures in the electron microscopy map and an IP₃ receptor-ryanodine receptor chimera consistently supported a coherent gating mechanism in these receptors. An intriguing feature was the long distance between the IP₃-binding sites and the Ca²⁺ channel, suggesting that long-range allosteric coupling occurs between these regions upon gating of the channel. These results help integrate previous knowledge on the IP₃ and ryanodine receptors and also provide a new framework for understanding the gating mechanism.
authors.affiliation: Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Hamada
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry* / Q000648:ultrastructure; D015640:Ion Channel Gating / Q000502:physiology*; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000648:ultrastructure; D013329:Structure-Activity Relationship
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D010446:Peptide Fragments; D019837:Ryanodine Receptor Calcium Release Channel