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Sci. STKE, 25 September 2007
Vol. 2007, Issue 405, p. tw345
[DOI: 10.1126/stke.4052007tw345]

EDITORS' CHOICE

Channels Gating ASICs

Elizabeth M. Adler

Science's STKE, AAAS, Washington, DC 20005, USA

Acid-sensing ion channels (ASICs) are members of a family of cation-selective ion channels that includes epithelial sodium channels and the degenerins, which shows a remarkable diversity of function and in the mechanisms of activation (see Canessa). Implicated in sensory perception, ASICs are sodium-selective and activated by extracellular protons independently of membrane potential. Jasti et al. combined crystallographic analysis with electrophysiology to explore the low-pH structure of {Delta}ASIC1, a chicken ASIC deletion mutant (in a desensitized nonconducting state), and investigated the mechanism underlying its pH-dependent gating. Unexpectedly, they found that {Delta}ASIC1 formed a homotrimer. Each subunit had two transmembrane helices and a large extracellular domain. Describing the overall domain structure of {Delta}ASIC1 subunits as resembling an "upright forearm and clenched hand" (with the extracellular domain constituting the "hand"), the authors identified a group of acidic residues as proton-binding sites that constitute the pH sensor. They suggest that proton binding leads to movement of the disulfide-rich thumb region, which transmits a long-range conformational change to allow the channel to open.

J. Jasti, H. Furukawa, E. B. Gonzales, E. Gouaux, Structure of acid-sensing ion channel 1 at 1.9 Å resolution and low pH. Nature 449, 316-323 (2007). [PubMed]

C. M. Canessa, Unexpected opening. Nature 449, 293-294 (2007). [PubMed]

Citation: E. M. Adler, Gating ASICs. Sci. STKE 2007, tw345 (2007).



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