| Structural highlights
Function
[ASIC1_CHICK] Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride (By similarity).[1] [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.[2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Coric T, Zheng D, Gerstein M, Canessa CM. Proton sensitivity of ASIC1 appeared with the rise of fishes by changes of residues in the region that follows TM1 in the ectodomain of the channel. J Physiol. 2005 Nov 1;568(Pt 3):725-35. Epub 2005 Jul 7. PMID:16002453 doi:http://dx.doi.org/jphysiol.2005.087734
- ↑ Escoubas P, De Weille JR, Lecoq A, Diochot S, Waldmann R, Champigny G, Moinier D, Menez A, Lazdunski M. Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels. J Biol Chem. 2000 Aug 18;275(33):25116-21. PMID:10829030 doi:http://dx.doi.org/10.1074/jbc.M003643200
- ↑ 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. Structure of the Acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1. Nat Commun. 2012 Jul 3;3:936. doi: 10.1038/ncomms1917. PMID:22760635 doi:10.1038/ncomms1917
|
