PMID:26458101

Citation	Fan, G, Baker, ML, Wang, Z, Baker, MR, Sinyagovskiy, PA, Chiu, W, Ludtke, SJ and Serysheva, II (2015) Gating machinery of InsP3R channels revealed by electron cryomicroscopy. Nature 527:336-41
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 Å) 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 ∼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 α-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.
Links	PubMed PMC4804758 Online version:10.1038/nature15249
Keywords	Allosteric Regulation; Animals; Apoproteins/chemistry; Apoproteins/metabolism; Apoproteins/ultrastructure; Calcium/metabolism; Calcium Signaling; Cryoelectron Microscopy; Cytosol/chemistry; Cytosol/metabolism; Inositol 1,4,5-Trisphosphate Receptors/chemistry; Inositol 1,4,5-Trisphosphate Receptors/metabolism; Inositol 1,4,5-Trisphosphate Receptors/ultrastructure; Ion Channel Gating; Models, Molecular; Protein Folding; Protein Structure, Quaternary; Protein Structure, Secondary; Protein Structure, Tertiary; Protein Subunits/chemistry; Protein Subunits/metabolism; Rats; Ryanodine Receptor Calcium Release Channel/chemistry; Ryanodine Receptor Calcium Release Channel/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:ITPR1	enables	GO:0042802: identical protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P29994-1	F		Seeded From UniProt	complete

References

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