Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, United Kingdom.
Cold Spring Harb Perspect Biol. 2010 Dec;2(12):a004010. doi: 10.1101/cshperspect.a004010. Epub 2010 Oct 27.
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.
三磷酸肌醇受体（IP3R）及其相关的兰尼碱受体是最常介导细胞内储存的 Ca2+释放的通道。它们通过 Ca2+的调节也能够再生性地传播细胞质 Ca2+信号。这篇简短的综述讨论了 IP3R 被 IP3 和 Ca2+激活的结构基础。IP3 通过促进 Ca2+与一个刺激 Ca2+结合位点的结合来启动 IP3R 的激活，但其身份尚未确定。我们认为，IP3 中关键磷酸基团与蛤壳样 IP3 结合核心的相对侧的相互作用导致其关闭，并通过相邻的 N 端抑制结构域将构象变化传播到孔道。由最后一对跨膜结构域和每个四联体 IP3R 亚基的孔环之间的孔道组装而成，形成一种结构，其中腔内选择性过滤器和孔道胞质末端的门控控制阳离子通过 IP3R 的流量。
