Abstract
SummaryAcid-sensing ion channels are proton-activated, sodium-selective channels composed of three subunits and members of the superfamily of epithelial sodium channels, mechanosensitive and FMRF peptide-gated ion channels. These ubiquitous eukaryotic ion channels play 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 describe the structure of a functional acid sensing ion channel in a desensitized state at 3 Å resolution, the location and composition of the ~8 Å ‘thick’ desensitization gate, and the trigonal antiprism coordination of cesium ions bound in the extracellular vestibule. Comparison of the acid sensing ion channel structure with the ATP-gated P2×4 receptor reveals similarity in pore architecture and aqueous vestibules, suggesting unanticipated yet common structural and mechanistic principles.
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