Inositol (1,4,5)-trisphosphate receptors (IP(3)R) are intracellular Ca(2+) channels that are regulated by Ca(2+) and IP(3), and are modulated by many additional signals. They thereby allow both receptors that stimulate IP(3) formation and Ca(2+) to control release of Ca(2+) from intracellular stores. IP(3)Rs share many features with their close relatives, ryanodine receptors; each provides insight into the structure and function of the other. The structural basis of IP(3)R behaviour is beginning to emerge from intermediate-resolution structures of the complete IP(3)R, a 2.2-A structure of the IP(3)-binding core and comparisons with the pore structures of other tetrameric cation channels. The binding of IP(3) to a site towards the N-terminal of each IP(3)R subunit promotes binding of Ca(2+). This destabilizes an inhibitory interaction between N-terminal residues and a C-terminal 'gatekeeper' sequence, enabling the pore to open.
