TY - JOUR
T1 - X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na+-selective channel
AU - Baconguis, Isabelle
AU - Bohlen, Christopher J.
AU - Goehring, April
AU - Julius, David
AU - Gouaux, Eric
N1 - Funding Information:
We thank members of the Gouaux lab and C. Jahr for helpful discussions, W. Lu for data processing, L. Vaskalis for figures, and H. Owen and J. Dieter for manuscript preparation. This work was supported by National Research Service Awards from the National Institute of Neurological Disorders and Stroke (I.B. and C.J.B.) and grants from the NIH (E.G. and D.J.). E.G. is an investigator with the Howard Hughes Medical Institute.
PY - 2014/2/13
Y1 - 2014/2/13
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2014.01.011
DO - 10.1016/j.cell.2014.01.011
M3 - Article
C2 - 24507937
AN - SCOPUS:84894105557
SN - 0092-8674
VL - 156
SP - 717
EP - 729
JO - Cell
JF - Cell
IS - 4
ER -