6DQZ

Class 4 IP3-bound human type 3 1,4,5-inositol trisphosphate receptor

This is a non-PDB format compatible entry.

Summary for 6DQZ

• Entry DOI: 10.2210/pdb6dqz/pdb
• EMDB information: 7978 7986
• Descriptor: Inositol 1,4,5-trisphosphate receptor type 3, ZINC ION, D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE (3 entities in total)
• Functional Keywords: ion channel, calcium channel, metal transport
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 1219896.77

Authors

Hite, R.K.,Paknejad, N. (deposition date: 2018-06-11, release date: 2018-08-01, Last modification date: 2024-10-16)

Primary citation

Paknejad, N.,Hite, R.K.
Structural basis for the regulation of inositol trisphosphate receptors by Ca2+and IP3.
Nat. Struct. Mol. Biol., 25:660-668, 2018

PubMed Abstract: Inositol trisphosphate receptors (IPRs) are ubiquitous Ca-permeable channels that mediate release of Ca from the endoplasmic reticulum, thereby regulating numerous processes including cell division, cell death, differentiation and fertilization. IPRs are jointly activated by inositol trisphosphate (IP) and their permeant ion, Ca. At high concentrations, however, Ca inhibits activity, ensuring precise spatiotemporal control over intracellular Ca. Despite extensive characterization of IPR, the mechanisms through which these molecules control channel gating have remained elusive. Here, we present structures of full-length human type 3 IPRs in ligand-bound and ligand-free states. Multiple IP-bound structures demonstrate that the large cytoplasmic domain provides a platform for propagation of long-range conformational changes to the ion-conduction gate. Structures in the presence of Ca reveal two Ca-binding sites that induce the disruption of numerous interactions between subunits, thereby inhibiting IPR. These structures thus provide a mechanistic basis for beginning to understand the regulation of IPR.

PubMed: 30013099
DOI: 10.1038/s41594-018-0089-6

Experimental method

ELECTRON MICROSCOPY (6.01 Å)