IP3 receptors: take four IP3 to open

摘要

Inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors are the channels responsible for Ca²⁺ release from the endoplasmic and sarcoplasmic reticulum. High-resolution structures of these enormous channels are beginning to reveal the inter-domain re-arrangements that link binding of their key regulators (IP3 and/or Ca²⁺) to opening of the Ca²⁺-permeable pore. Activation of IP3R is initiated when IP3 causes its clam-like binding domain to close, thereby disrupting interactions with other domains that may then communicate with the pore. All four IP3-binding sites within the tetrameric IP3R must bind IP3 before the channel can open. This has important consequences for the distribution of both IP3 and IP3R activity within cells, and it may contribute to the complex spatial organization of intracellular Ca²⁺ signals.