2QTS

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

Summary for 2QTS

• Entry DOI: 10.2210/pdb2qts/pdb
• Related PRD ID: PRD_900001
• Descriptor: Acid-sensing ion channel, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: acid-sensing, ion channel, trimer, membrane protein
• Biological source: Gallus gallus (chicken)
• Total number of polymer chains: 6
• Total formula weight: 304818.62

Authors

Jasti, J.,Furukawa, H.,Gonzales, E.B.,Gouaux, E. (deposition date: 2007-08-02, release date: 2007-09-25, Last modification date: 2024-10-30)

Primary citation

Jasti, J.,Furukawa, H.,Gonzales, E.B.,Gouaux, E.
Structure of acid-sensing ion channel 1 at 1.9A resolution and low pH
Nature, 449:316-323, 2007

PubMed 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.

PubMed: 17882215
DOI: 10.1038/nature06163

Experimental method

X-RAY DIFFRACTION (1.9 Å)