3JAV: Structure Of Full-length Ip3r1 Channel In The Apo-state Determined By Single Particle Cryo-em

Citation:
Abstract
Inositol-1,4,5-trisphosphate receptors (InsP3Rs) are ubiquitous ion channels responsible for cytosolic Ca(2+) signalling and essential for a broad array of cellular processes ranging from contraction to secretion, and from proliferation to cell death. Despite decades of research on InsP3Rs, a mechanistic understanding of their structure-function relationship is lacking. Here we present the first, to our knowledge, near-atomic (4.7 A) resolution electron cryomicroscopy structure of the tetrameric mammalian type 1 InsP3R channel in its apo-state. At this resolution, we are able to trace unambiguously approximately 85% of the protein backbone, allowing us to identify the structural elements involved in gating and modulation of this 1.3-megadalton channel. Although the central Ca(2+)-conduction pathway is similar to other ion channels, including the closely related ryanodine receptor, the cytosolic carboxy termini are uniquely arranged in a left-handed alpha-helical bundle, directly interacting with the amino-terminal domains of adjacent subunits. This configuration suggests a molecular mechanism for allosteric regulation of channel gating by intracellular signals.
PDB ID: 3JAVDownload
MMDB ID: 133598
PDB Deposition Date: 2015/6/30
Updated in MMDB: 2015/12
Experimental Method:
electron microscopy
Resolution: 4.7  Å
Source Organism:
Similar Structures:
Biological Unit for 3JAV: tetrameric; determined by author
Molecular Components in 3JAV
Label Count Molecule
Proteins (4 molecules)
4
Inositol 1,4,5-trisphosphate Receptor Type 1(Gene symbol: Itpr1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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