Referenced in: none

Automatically associated channels: Kir2.3

Title: On the Putative Binding Site of RFamide-Family Neuropeptides from the Western Atlantic Clam Sunray Venus and Cephalopods on Acid-Sensing Ion Channels. An Automated Docking and Molecular-Dynamics Study with hASIC1a Homology Model.

Authors: Francesco Pietra

Journal, date & volume: Chem. Biodivers., 2011 May , 8, 816-26

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21560230

Abstract
Investigated here are interactions of C-terminal amidated peptides with the hASIC1a acid-sensing ion channel. The peptides comprise endogenous FMRFa, present in the western Atlantic clam Sunray Venus, and FIRFa, present in cephalopods, as well as non-endogenous ones for comparison. The interaction is investigated by automated docking. The resulting key hASIC1a-FMRFa complex, set in a lipidic POPC (=1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) membrane surrounded by H(2) O and Na(+) -neutralized, was also investigated by molecular dynamics. It was observed that all investigated peptides become encapsulated into the ion channel, on one side by the thumb and finger of a subunit, and, on the opposite side, by the knuckle and β-ball of a second subunit. The third subunit is not involved. This is much the same binding site that was disclosed previously by both a similar computational approach, and electrophysiological and binding experiments for the hASIC1a ion channel-blocker tarantula toxin PCTX1. This paves the way to a better understanding of the role of these peptides in invertebrates.