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2ndi

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Solution structure of the toxin ISTX-I from Ixodes scapularis

Structural highlights

2ndi is a 1 chain structure with sequence from Ixodes scapularis. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ISTX_IXOSC By inhibiting Nav1.7/SCN9A sodium channel, may prevent signal transmission caused by tick penetration and the blood taken, allowing the tick to avoid discovery (PubMed:27407029). Weakly and specifically inhibits Nav1.7/SCN9A (IC(50)=1.6 uM) (PubMed:27407029). Significantly shifts the steady-state inactivation curve of the Nav1.7/SCN9A in the hyperpolarized direction (PubMed:27407029). Does not induce changes to I-V curve and conductance-voltage relationship (PubMed:27407029).^[1]

Publication Abstract from PubMed

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 inhibitor cystine 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 muM 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.

A sodium channel inhibitor ISTX-I with a novel structure provides a new hint at the evolutionary link between two toxin folds.,Rong M, Liu J, Zhang M, Wang G, Zhao G, Wang G, Zhang Y, Hu K, Lai R Sci Rep. 2016 Jul 13;6:29691. doi: 10.1038/srep29691. PMID:27407029^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rong M, Liu J, Zhang M, Wang G, Zhao G, Wang G, Zhang Y, Hu K, Lai R. A sodium channel inhibitor ISTX-I with a novel structure provides a new hint at the evolutionary link between two toxin folds. Sci Rep. 2016 Jul 13;6:29691. doi: 10.1038/srep29691. PMID:27407029 doi:http://dx.doi.org/10.1038/srep29691
↑ Rong M, Liu J, Zhang M, Wang G, Zhao G, Wang G, Zhang Y, Hu K, Lai R. A sodium channel inhibitor ISTX-I with a novel structure provides a new hint at the evolutionary link between two toxin folds. Sci Rep. 2016 Jul 13;6:29691. doi: 10.1038/srep29691. PMID:27407029 doi:http://dx.doi.org/10.1038/srep29691