Novel αD-Conopeptides and Their Precursors Identified by cDNA Cloning Define the D-Conotoxin Superfamily

摘要

RD-Conotoxins are peptide inhibitors of nicotinic acetylcholine receptors (nAChRs) firstndescribed from Conus Vexillum (RD-VxXIIA-C and renamed here to RD-VxXXA, RD-VxXXB, andnRD-VxXXC). In this study, we report cDNA sequences encoding D-superfamily conopeptides identifiednin the Clade XII Conidae Conus Vexillum, Conus capitaneus, Conus mustelinus, and Conus miles, togethernwith partial sequences of corresponding peptides from this family. The D-superfamily signal peptidensequences display greater heterogeneity than reported for other conotoxin superfamilies. Phylogeneticnanalysis of the relationships among RD-conotoxin precursors reveals two distinct groups containing eithernan EMM or AVV signal peptide sequence motif. Homodimer and heterodimer combinations of predictednmature toxin sequences likely account for the partial amino acid sequences and mass values observed fornseveral of the native dimeric peptide components identified in C. capitaneus, C. miles, and C. mustelinusnvenom. The discovery of the precursors and several novel conotoxins from different species defines thisnlarge conotoxin family and expands our understanding of sequence diversification mechanisms in Conusnspecies.