Evolutionary origin of inhibitor cystine knot peptides

SPECIFIC AIMSThe inhibitor cystine knot (ICK) fold is an evolutionarily conserved structural motif shared by a large group of polypeptides with diverse sequences and functions. Although found in different phyla (animal, plant, and fungus), ICK peptides appear to be most prominent in venoms of cone snail and spider. Recently, two scorpion toxins activating a calcium release channel were also characterized to adopt an ICK fold. The evolutionary relationship among these peptides, however, has not been elucidated to date. Structural similarity often provides evidence to support a divergent evolution mechanism, but structural convergence is not completely ruled out in this case. We isolated and identified full-length cDNAs encoding two new members of the scorpion venom ICK toxin family and determined the first complete gene structure of this family. Together, our data provide compelling evidence to trace the evolutionary process of ICK peptides. By analyzing the precursor organization and gene structure combin...