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

Isabelle Baconguis, Christopher J. Bohlen, April Goehring, David Julius, Eric Gouaux

Research output: Contribution to journalArticle

136 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)717-729
Number of pages13
JournalCell
Volume156
Issue number4
DOIs
StatePublished - Feb 13 2014

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Acid Sensing Ion Channels
Snakes
Degenerin Sodium Channels
X-Rays
Epithelial Sodium Channels
Elapidae
X rays
Sodium Channels
Ion Channels
Conformations
Protons
Chickens
Sodium
Ions
Oxygen
Inflammation
Pain
Atoms
Wounds and Injuries
Electric potential

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na+-selective channel. / Baconguis, Isabelle; Bohlen, Christopher J.; Goehring, April; Julius, David; Gouaux, Eric.

In: Cell, Vol. 156, No. 4, 13.02.2014, p. 717-729.

Research output: Contribution to journalArticle

Baconguis, Isabelle ; Bohlen, Christopher J. ; Goehring, April ; Julius, David ; Gouaux, Eric. / X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na+-selective channel. In: Cell. 2014 ; Vol. 156, No. 4. pp. 717-729.
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