Structural highlights
Function[ITPR3_HUMAN] Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. Publication Abstract from PubMedA pivotal component of the calcium (Ca(2+)) signaling toolbox in cells is the inositol 1,4,5-triphosphate (IP3) receptor (IP3R), which mediates Ca(2+) release from the endoplasmic reticulum (ER), controlling cytoplasmic and organellar Ca(2+) concentrations. IP3Rs are co-activated by IP3 and Ca(2+), inhibited by Ca(2+) at high concentrations, and potentiated by ATP. However, the underlying molecular mechanisms are unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human type-3 IP3R obtained from a single dataset in multiple gating conformations: IP3-ATP bound pre-active states with closed channels, IP3-ATP-Ca(2+) bound active state with an open channel, and IP3-ATP-Ca(2+) bound inactive state with a closed channel. The structures demonstrate how IP3-induced conformational changes prime the receptor for activation by Ca(2+), how Ca(2+) binding leads to channel opening, and how ATP modulates the activity, providing insights into the long-sought questions regarding the molecular mechanism underpinning receptor activation and gating. Structural basis for activation and gating of IP3 receptors.,Schmitz EA, Takahashi H, Karakas E Nat Commun. 2022 Mar 17;13(1):1408. doi: 10.1038/s41467-022-29073-2. PMID:35301323[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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