X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel

Cell. 2014 Feb 13;156(4):717-29. doi: 10.1016/j.cell.2014.01.011. Epub 2014 Feb 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels / chemistry*
  • Acid Sensing Ion Channels / metabolism
  • Amino Acid Sequence
  • Animals
  • Avian Proteins / chemistry*
  • Avian Proteins / metabolism
  • Chickens*
  • Crystallography, X-Ray
  • Elapid Venoms / chemistry*
  • Elapid Venoms / metabolism
  • Elapidae*
  • Models, Molecular
  • Molecular Sequence Data
  • Sequence Alignment
  • Sodium Channels / chemistry


  • Acid Sensing Ion Channels
  • Avian Proteins
  • Elapid Venoms
  • Sodium Channels

Associated data

  • PDB/4NTW
  • PDB/4NTX
  • PDB/4NTY