4NTX

Structure of acid-sensing ion channel in complex with snake toxin and amiloride

Summary for 4NTX

• Entry DOI: 10.2210/pdb4ntx/pdb
• Related: 2QTS 3HGC 4FZ0 4NTW 4NTY 4NYK
• Descriptor: Acid-sensing ion channel 1, Neurotoxin MitTx-alpha, Basic phospholipase A2 homolog Tx-beta, ... (9 entities in total)
• Functional Keywords: kunitz, phospholipase a2-like, ion channel, nociception, membrane, transport protein-toxin complex, transport protein/toxin
• Biological source: Gallus gallus (bantam,chickens); More
• Total number of polymer chains: 3
• Total formula weight: 73731.02

Authors

Baconguis, I.,Bohlen, C.J.,Goehring, A.,Julius, D.,Gouaux, E. (deposition date: 2013-12-02, release date: 2014-02-19, Last modification date: 2024-10-30)

Primary citation

Baconguis, I.,Bohlen, C.J.,Goehring, A.,Julius, D.,Gouaux, E.
X-ray structure of Acid-sensing ion channel 1-snake toxin complex reveals open state of a na(+)-selective channel.
Cell(Cambridge,Mass.), 156:717-729, 2014

PubMed 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.

PubMed: 24507937
DOI: 10.1016/j.cell.2014.01.011

Experimental method

X-RAY DIFFRACTION (2.27 Å)