Glycosylation Increases the Thermostability of Human Aquaporin 10

Venom-derived peptide toxins, that modify the gating characteristics of ion channels without directly blocking the ion permeation pathway, were important tools for understanding ion channel function.However how these toxins interact with the channels and their exact molecular mechanism is still unknown.We solved the crystal structure of the trimeric chicken Acid-sensing ion channel 1 (ASIC1) in complex with the highly selective gating modifier Psalmotoxin 1 (PcTx1) at 3.0 Å resolution.The structure shows three toxin molecules binding at the proton-sensitive acidic pockets of the ASIC1-trimer and details the molecular interactions that convey the toxins high potency and selectivity.PcTx1 binding locks two separate regulatory regions on the channel in their relative, desensitized-like arrangement.Consequently electron density is observed, that is consistent with a cation trapped above the ion pathway in the channel's central vestibule.A hydrophobic patch and a basic cluster are the key surface motifs of PcTx1 used for interacting with ASIC1.Because these motifs are also present on other gating modifier toxins, our results provide a general concept for gating modifier toxin mechanism.