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

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 A 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 A, 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.

• Authors: Jayasankar Jasti, Hiroyasu Furukawa, Eric B Gonzales, Eric Gouaux
• Journal: Nature (Nature) Vol. 449 Issue 7160 Pg. 316-23 (Sep 20 2007) ISSN: 1476-4687 [Electronic] England
• PMID: 17882215 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Acid Sensing Ion Channels
• Chlorides
• Membrane Proteins
• Nerve Tissue Proteins
• Protein Subunits
• Protons
• Sodium Channels

Topics

• Acid Sensing Ion Channels
• Animals
• Binding Sites
• Cell Line
• Chickens (genetics)
• Chlorides (metabolism)
• Crystallography, X-Ray
• Hydrogen-Ion Concentration
• Membrane Proteins (chemistry, genetics, metabolism)
• Models, Molecular
• Nerve Tissue Proteins (chemistry, genetics, metabolism)
• Protein Binding
• Protein Structure, Quaternary
• Protein Structure, Tertiary
• Protein Subunits (chemistry, metabolism)
• Protons
• Sequence Deletion
• Sodium Channels (chemistry, genetics, metabolism)
• Structure-Activity Relationship