Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus

FEBS Letters
P K PallaghyRaymond S Norton

Abstract

The solution structure of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, has been determined from 2D 1H NMR data. Robustoxin is a polypeptide of 42 residues cross-linked by four disulphide bonds, the connectivities of which were determined from NMR data and trial structure calculations to be 1-15, 8-20, 14-31 and 16-42 (a 1-4/2-6/3-7/5-8 pattern). The structure consists of a small three-stranded, anti-parallel beta-sheet and a series of interlocking gamma-turns at the C-terminus. It also contains a cystine knot, thus placing it in the inhibitor cystine knot motif family of structures, which includes the omega-conotoxins and a number of plant and animal toxins and protease inhibitors. Robustoxin contains three distinct charged patches on its surface, and an extended loop that includes several aromatic and non-polar residues. Both of these structural features may play a role in its binding to the voltage-gated sodium channel.

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Citations

Feb 17, 2001·Biopolymers·M D LaniganR S Norton
Apr 7, 2004·Toxicon : Official Journal of the International Society on Toxinology·Graham M NicholsonLiesl C Birinyi-Strachan
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