3s3x

Structure of chicken acid-sensing ion channel 1 AT 3.0 A resolution in complex with psalmotoxin

spinqualitylabelsall models 3s3x, resolution 2.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3s3x is a 6 chain structure with sequence from Chick. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, K, NAG, SO4 Related: 3s3w Gene: ACCN2, ASIC1 (CHICK) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ASIC1_CHICK] Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride (By similarity). [TXP1_PSACA] Potently and selectively blocks the acid-sensing ion channel ASIC1a/ACCN2. The blockade is rapid and reversible. Psalmotoxin 1 loses its capacity to block ASIC1a/ACCN2 as soon as this subunit is associated with another member of the family (ASIC2a/ACCN1 or ASIC3/ACCN3). The toxin can distinguish between the two ASIC1/ACCN2 splice variants ASIC1a/ACCN2 and ASIC1b/ACCN2. Publication Abstract from PubMed Venom-derived peptide toxins can modify the gating characteristics of excitatory channels in neurons. How they bind and interfere with the flow of ions without directly blocking the ion permeation pathway remains elusive. Here we report the crystal structure of the trimeric chicken Acid-sensing ion channel 1 in complex with the highly selective gating modifier Psalmotoxin 1 at 3.0 A resolution. The structure reveals the molecular interactions of three toxin molecules binding at the proton-sensitive acidic pockets of Acid-sensing ion channel 1 and electron density consistent with a cation trapped in the central vestibule above the ion pathway. A hydrophobic patch and a basic cluster are the key structural elements of Psalmotoxin 1 binding, locking two separate regulatory regions in their relative, desensitized-like arrangement. Our results provide a general concept for gating modifier toxin binding suggesting that both surface motifs are required to modify the gating characteristics of an ion channel. Structure of the Acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1.,Dawson RJ, Benz J, Stohler P, Tetaz T, Joseph C, Huber S, Schmid G, Hugin D, Pflimlin P, Trube G, Rudolph MG, Hennig M, Ruf A Nat Commun. 2012 Jul 3;3:936. doi: 10.1038/ncomms1917. PMID:22760635 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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