3JAV

Structure of full-length IP3R1 channel in the apo-state determined by single particle cryo-EM

Summary for 3JAV

• Entry DOI: 10.2210/pdb3jav/pdb
• EMDB information: 6369
• Descriptor: Inositol 1,4,5-trisphosphate receptor type 1 (1 entity in total)
• Functional Keywords: inositol 1, 4, 5-trisphosphate receptor, calcium release channel, calcium signaling, transport protein
• Biological source: Rattus norvegicus (rat)
• Total number of polymer chains: 4
• Total formula weight: 1254629.62

Authors

Fan, G.,Baker, M.L.,Wang, Z.,Baker, M.R.,Sinyagovskiy, P.A.,Chiu, W.,Ludtke, S.J.,Serysheva, I.I. (deposition date: 2015-06-30, release date: 2015-10-07, Last modification date: 2024-02-21)

Primary citation

Fan, G.,Baker, M.L.,Wang, Z.,Baker, M.R.,Sinyagovskiy, P.A.,Chiu, W.,Ludtke, S.J.,Serysheva, I.I.
Gating machinery of InsP3R channels revealed by electron cryomicroscopy.
Nature, 527:336-341, 2015

PubMed 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.

PubMed: 26458101
DOI: 10.1038/nature15249

Experimental method

ELECTRON MICROSCOPY (4.7 Å)