Structure of acid-sensing ion channel 1 at 1.9 Å resolution and low pH

Jayasankar Jasti, Hiroyasu Furukawa, Eric B. Gonzales, Eric Gouaux

Research output: Contribution to journalArticle

719 Citations (Scopus)

Abstract

Acid-sensing ion channels (ASICs) are voltage-independent, proton-activated receptors that belong to the epithelial sodium channel/degenerin family of ion channels and are implicated in perception of pain, ischaemic stroke, mechanosensation, learning and memory. Here we report the low-pH crystal structure of a chicken ASIC1 deletion mutant at 1.9 Å resolution. Each subunit of the chalice-shaped homotrimer is composed of short amino and carboxy termini, two transmembrane helices, a bound chloride ion and a disulphide-rich, multidomain extracellular region enriched in acidic residues and carboxyl-carboxylate pairs within 3 Å, suggesting that at least one carboxyl group bears a proton. Electrophysiological studies on aspartate-to-asparagine mutants confirm that these carboxyl-carboxylate pairs participate in proton sensing. Between the acidic residues and the transmembrane pore lies a disulphide-rich 'thumb' domain poised to couple the binding of protons to the opening of the ion channel, thus demonstrating that proton activation involves long-range conformational changes.

Original languageEnglish (US)
Pages (from-to)316-323
Number of pages8
JournalNature
Volume449
Issue number7160
DOIs
StatePublished - Sep 20 2007

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Acid Sensing Ion Channels
Protons
Disulfides
Degenerin Sodium Channels
Epithelial Sodium Channels
Pain Perception
Asparagine
Thumb
Ion Channels
Aspartic Acid
Chlorides
Chickens
Stroke
Learning
Ions

ASJC Scopus subject areas

  • General

Cite this

Structure of acid-sensing ion channel 1 at 1.9 Å resolution and low pH. / Jasti, Jayasankar; Furukawa, Hiroyasu; Gonzales, Eric B.; Gouaux, Eric.

In: Nature, Vol. 449, No. 7160, 20.09.2007, p. 316-323.

Research output: Contribution to journalArticle

Jasti, Jayasankar ; Furukawa, Hiroyasu ; Gonzales, Eric B. ; Gouaux, Eric. / Structure of acid-sensing ion channel 1 at 1.9 Å resolution and low pH. In: Nature. 2007 ; Vol. 449, No. 7160. pp. 316-323.
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