title: X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel.
abstract: Acid-sensing ion channels (ASICs) detect extracellular protons produced during inflammation or ischemic injury and belong to the superfamily of degenerin/epithelial sodium channels. Here, we determine the cocrystal structure of chicken ASIC1a with MitTx, a pain-inducing toxin from the Texas coral snake, to define the structure of the open state of ASIC1a. In the MitTx-bound open state and in the previously determined low-pH desensitized state, TM2 is a discontinuous α helix in which the Gly-Ala-Ser selectivity filter adopts an extended, belt-like conformation, swapping the cytoplasmic one-third of TM2 with an adjacent subunit. Gly 443 residues of the selectivity filter provide a ring of three carbonyl oxygen atoms with a radius of ∼3.6 Å, presenting an energetic barrier for hydrated ions. The ASIC1a-MitTx complex illuminates the mechanism of MitTx action, defines the structure of the selectivity filter of voltage-independent, sodium-selective ion channels, and captures the open state of an ASIC.
authors: Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors: Isabelle
authors: I
authors: Baconguis
authors: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors: Christopher J
authors: CJ
authors: Bohlen
authors: Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors: April
authors: A
authors: Goehring
authors: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors: David
authors: D
authors: Julius
authors: Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA; Howard Hughes Medical Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Electronic address: gouauxe@ohsu.edu.
authors: Eric
authors: E
authors: Gouaux
mesh_terms: D062565:Acid Sensing Ion Channels / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry* / Q000378:metabolism; D002645:Chickens; D018360:Crystallography, X-Ray; D004546:Elapid Venoms / Q000737:chemistry* / Q000378:metabolism; D017815:Elapidae; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D015222:Sodium Channels / Q000737:chemistry
chemical_list: D062565:Acid Sensing Ion Channels; D030161:Avian Proteins; D004546:Elapid Venoms; D015222:Sodium Channels