A  sodium  channel  inhibitor  ISTX-I with  a  novel structure provides a new hint at the evolutionary link betwee-n two toxin folds. Sci Rep, 2016, 6: 29691 

Title: A sodium channel inhibitor ISTX-I with a novel structure provides a new hint at the evolutionary link between two toxin foldsA sodium channel inhibitor ISTX-I with a novel structure provides a new hint at the evolutionary link between two toxin folds. 

Author: Rong M, Liu J, Zhang M, Wang G, Zhao G, Wang G, Zhang Y, Hu K, Lai R

Publication Name: Sci Rep 

Pub Year: 2016

Volume: 6 

Issue:

Page Number: 29691

IF: 5.228

Abstract:

Members of arachnida, such as spiders and scorpions, commonly produce venom with specialized venom glands, paralyzing their prey with neurotoxins that specifically target ion channels. Two well-studied motifs, the disulfide-directed hairpin (DDH) and the inhibitorcystine knot motif (ICK), are both found in scorpion and spider toxins. As arachnids, ticks inject a neurotoxin-containing cocktail from their salivary glands into the host to acquire a blood meal, but peptide toxins acting on ion channels have not been observed in ticks. Here, a new neurotoxin (ISTX-I) that acts on sodium channels was identified from the hard tick Ixodes scapularis and characterized.ISTX-I exhibits a potent inhibitory function with an IC50 of 1.6 μM for sodium channel Nav1.7 but not other sodium channel subtypes.ISTX-I adopts a novel structural fold and is distinct from the canonical ICK motif. Analysis of the ISTX-I, DDH and ICK motifs reveals that the new ISTX-I motif might be an intermediate scaffold between DDH and ICK, and ISTX-I is a clue to the evolutionary link between the DDH and ICK motifs. These results provide a glimpse into the convergent evolution of neurotoxins from predatory and blood-sucking arthropods.