title: IP(3) receptors: toward understanding their activation.
abstract: Inositol 1,4,5-trisphosphate receptors (IP(3)R) and their relatives, ryanodine receptors, are the channels that most often mediate Ca(2+) release from intracellular stores. Their regulation by Ca(2+) allows them also to propagate cytosolic Ca(2+) signals regeneratively. This brief review addresses the structural basis of IP(3)R activation by IP(3) and Ca(2+). IP(3) initiates IP(3)R activation by promoting Ca(2+) binding to a stimulatory Ca(2+)-binding site, the identity of which is unresolved. We suggest that interactions of critical phosphate groups in IP(3) with opposite sides of the clam-like IP(3)-binding core cause it to close and propagate a conformational change toward the pore via the adjacent N-terminal suppressor domain. The pore, assembled from the last pair of transmembrane domains and the intervening pore loop from each of the four IP(3)R subunits, forms a structure in which a luminal selectivity filter and a gate at the cytosolic end of the pore control cation fluxes through the IP(3)R.
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, United Kingdom. cwt1000@cam.ac.uk
authors.forename: Colin W
authors.initials: CW
authors.lastname: Taylor
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Tovey
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D008958:Models, Molecular; D010710:Phosphates / Q000378:metabolism; D011487:Protein Conformation; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D010710:Phosphates; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium