PUBLICATION
Crystal structure of the ATP-gated P2X(4) ion channel in the closed state
- Authors
- Kawate, T., Michel, J.C., Birdsong, W.T., and Gouaux, E.
- ID
- ZDB-PUB-090731-18
- Date
- 2009
- Source
- Nature 460(7255): 592-598 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Adenosine Triphosphate/metabolism
- Animals
- Binding Sites
- Cell Line
- Crystallography, X-Ray
- Gadolinium/metabolism
- Humans
- Ion Channels/antagonists & inhibitors
- Ion Channels/chemistry*
- Membrane Proteins/chemistry
- Models, Molecular*
- Protein Binding
- Protein Folding
- Protein Structure, Tertiary
- Purinergic P2 Receptor Antagonists
- Receptors, Purinergic P2/chemistry*
- Receptors, Purinergic P2X4
- Zebrafish/physiology*
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/chemistry*
- PubMed
- 19641588 Full text @ Nature
Citation
Kawate, T., Michel, J.C., Birdsong, W.T., and Gouaux, E. (2009) Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature. 460(7255):592-598.
Abstract
P2X receptors are cation-selective ion channels gated by extracellular ATP, and are implicated in diverse physiological processes, from synaptic transmission to inflammation to the sensing of taste and pain. Because P2X receptors are not related to other ion channel proteins of known structure, there is at present no molecular foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation. Here we present crystal structures of the zebrafish P2X(4) receptor in its closed, resting state. The chalice-shaped, trimeric receptor is knit together by subunit-subunit contacts implicated in ion channel gating and receptor assembly. Extracellular domains, rich in beta-strands, have large acidic patches that may attract cations, through fenestrations, to vestibules near the ion channel. In the transmembrane pore, the 'gate' is defined by an approximately 8 A slab of protein. We define the location of three non-canonical, intersubunit ATP-binding sites, and suggest that ATP binding promotes subunit rearrangement and ion channel opening.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping