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.
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.
authors.affiliation: Accademia Lucchese di Scienze, Lettere e Arti, Classe di Scienze, Palazzo Ducale, Lucca. francesco.pietra@accademialucchese.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Pietra
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D001665:Binding Sites; D049872:Bivalvia / Q000737:chemistry / Q000378:metabolism*; D049830:Cephalopoda / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*
chemical_list: D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D015222:Sodium Channels