Structure of the Acid-sensing ion channel 1 incomplex with the gating modifier Psalmotoxin 1

摘要

Venom-derived peptide toxins can modify the gating characteristics of excitatory channels inneurons. How they bind and interfere with the flow of ions without directly blocking the ionpermeation pathway remains elusive. Here we report the crystal structure of the trimeric chickenAcid-sensing ion channel 1 in complex with the highly selective gating modifier Psalmotoxin 1at 3.0 A resolution. The structure reveals the molecular interactions of three toxin moleculesbinding at the proton-sensitive acidic pockets of Acid-sensing ion channel 1 and electron densityconsistent with a cation trapped in the central vestibule above the ion pathway. A hydrophobicpatch and a basic cluster are the key structural elements of Psalmotoxin 1 binding, locking twoseparate regulatory regions in their relative, desensitized-like arrangement. Our results providea general concept for gating modifier toxin binding suggesting that both surface motifs arerequired to modify the gating characteristics of an ion channel.