7T3U

IP3, ATP, and Ca2+ bound type 3 IP3 receptor in the inactive state

Summary for 7T3U

• Entry DOI: 10.2210/pdb7t3u/pdb
• Related: 7T3P 7T3Q 7T3R 7T3T
• EMDB information: 25671
• Descriptor: Inositol 1,4,5-trisphosphate receptor type 3, ZINC ION, D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: ip3 receptor, calcium signaling, metal transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 1200594.36

Authors

Schmitz, E.A.,Takahashi, H.,Karakas, E. (deposition date: 2021-12-08, release date: 2022-03-23, Last modification date: 2022-05-04)

Primary citation

Schmitz, E.A.,Takahashi, H.,Karakas, E.
Structural basis for activation and gating of IP 3 receptors.
Nat Commun, 13:1408-1408, 2022

PubMed Abstract: A pivotal component of the calcium (Ca) signaling toolbox in cells is the inositol 1,4,5-triphosphate (IP) receptor (IPR), which mediates Ca release from the endoplasmic reticulum (ER), controlling cytoplasmic and organellar Ca concentrations. IPRs are co-activated by IP and Ca, inhibited by Ca 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 IPR obtained from a single dataset in multiple gating conformations: IP-ATP bound pre-active states with closed channels, IP-ATP-Ca bound active state with an open channel, and IP-ATP-Ca bound inactive state with a closed channel. The structures demonstrate how IP-induced conformational changes prime the receptor for activation by Ca, how Ca 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.

PubMed: 35301323
DOI: 10.1038/s41467-022-29073-2

Experimental method

ELECTRON MICROSCOPY (3.7 Å)