PDBsum entry 4ntx

Transport protein/toxin

PDB id: 4ntx

Contents

Protein chains

410 a.a.

60 a.a.

118 a.a.

Ligands

NAG ×2

P6G

AMR ×3

Metals

_NA ×3

_CL

Waters ×180

PDB id:

4ntx

Name:

Transport protein/toxin

Title:

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

Structure:

Acid-sensing ion channel 1. Chain: a. Fragment: unp residues 14-463. Synonym: asic1, amiloride-sensitive cation channel 2, neuronal. Engineered: yes. Neurotoxin mittx-alpha. Chain: b. Engineered: yes. Basic phospholipase a2 homolog tx-beta.

Source:

Gallus gallus. Bantam,chickens. Organism_taxid: 9031. Gene: asic1, accn2. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: human embryonic kidney cells. Micrurus tener tener. Texas coral snake.

Resolution:

2.27Å R-factor: 0.207 R-free: 0.233

Authors:

I.Baconguis,C.J.Bohlen,A.Goehring,D.Julius,E.Gouaux

Key ref:

I.Baconguis et al. (2014). X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel. Cell, 156, 717-729. PubMed id: 24507937 DOI: 10.1016/j.cell.2014.01.011

Date:

02-Dec-13 Release date: 19-Feb-14

Protein chain

Q1XA76  (ASIC1_CHICK) -  Acid-sensing ion channel 1 from Gallus gallus

Seq: 527 a.a.

Struc: 410 a.a.

Protein chain

G9I929  (VKTA_MICTN) -  Kunitz-type neurotoxin MitTx-alpha from Micrurus tener tener

Seq: 84 a.a.

Struc: 60 a.a.*

Protein chain

G9I930  (PA2HB_MICTN) -  Basic phospholipase A2 homolog MitTx-beta from Micrurus tener tener

Seq: 149 a.a.

Struc: 118 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.cell.2014.01.011

Cell 156:717-729 (2014)

PubMed id: 24507937

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

I.Baconguis, C.J.Bohlen, A.Goehring, D.Julius, E.Gouaux.

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.