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

Jasti, J., Furukawa, H., Gonzales, E. B., Gouaux, E. (2007) Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH. Nature, 449 (7160). pp. 316-23. ISSN 1476-4687 (Electronic) 1476-4687 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/17882215
DOI: 10.1038/nature06163

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.

Item Type: Paper
Uncontrolled Keywords: 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
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > ion channel
Investigative techniques and equipment > x ray crystallography
CSHL Authors:
Communities: CSHL labs > Furukawa lab
Depositing User: CSHL Librarian
Date Deposited: 14 Nov 2011 19:32
Last Modified: 08 Sep 2017 16:07
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Dataset ID:
URI: http://repository.cshl.edu/id/eprint/23051

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