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X-Ray Structure of Acid-Sensing Ion Channel 1–Snake Toxin Complex Reveals Open State of a Na+-Selective Channel

Open access
Baconguis, Isabelle, Bohlen, Christopher J., Goehring, April, Julius, David, Gouaux, Eric·2014·Cell

Abstract

Summary Acid sensing ion channels (ASICs) detect extracellular protons produced during inflammation or ischemic injury and belong to the super family 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 3 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.

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Crossref · 10.1016/j.cell.2014.01.011

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Metadata

Authors
Baconguis, I., Bohlen, C. J., Goehring, A., Julius, D., & Gouaux, E.
Venue
Cell
Publisher
Elsevier BV
Published
2014-02
Volume
156
Issue
4
Pages
717-729
ISSN
0092-8674 (ISSN-L)
OpenAlex
W1974548955
Cited by
286
References
2
FWCI
10.59
Type
journal article
Language
en
Open access
bronze

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