Pore architecture and ion sites in acid-sensing ion channels and P2X receptors

Eric B. Gonzales, Toshimitsu Kawate, Eric Gouaux

Research output: Contribution to journalArticle

292 Citations (Scopus)

Abstract

Acid-sensing ion channels are proton-activated, sodium-selective channels composed of three subunits, and are members of the superfamily of epithelial sodium channels, mechanosensitive and FMRF-amide peptide-gated ion channels. These ubiquitous eukaryotic ion channels have essential roles in biological activities as diverse as sodium homeostasis, taste and pain. Despite their crucial roles in biology and their unusual trimeric subunit stoichiometry, there is little knowledge of the structural and chemical principles underlying their ion channel architecture and ion-binding sites. Here we present the structure of a functional acid-sensing ion channel in a desensitized state at 3 resolution, the location and composition of the 8 thick desensitization gate, and the trigonal antiprism coordination of caesium ions bound in the extracellular vestibule. Comparison of the acid-sensing ion channel structure with the ATP-gated P2X 4 receptor reveals similarity in pore architecture and aqueous vestibules, suggesting that there are unanticipated yet common structural and mechanistic principles.

Original languageEnglish (US)
Pages (from-to)599-604
Number of pages6
JournalNature
Volume460
Issue number7255
DOIs
StatePublished - Jul 30 2009

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Acid Sensing Ion Channels
Ion Channels
Ions
FMRFamide
Epithelial Sodium Channels
Cesium
Sodium Channels
Protons
Homeostasis
Adenosine Triphosphate
Sodium
Binding Sites
Pain
Peptides

ASJC Scopus subject areas

  • General

Cite this

Pore architecture and ion sites in acid-sensing ion channels and P2X receptors. / Gonzales, Eric B.; Kawate, Toshimitsu; Gouaux, Eric.

In: Nature, Vol. 460, No. 7255, 30.07.2009, p. 599-604.

Research output: Contribution to journalArticle

Gonzales, Eric B. ; Kawate, Toshimitsu ; Gouaux, Eric. / Pore architecture and ion sites in acid-sensing ion channels and P2X receptors. In: Nature. 2009 ; Vol. 460, No. 7255. pp. 599-604.
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