The three-dimensional structure of scorpion neurotoxins

Abstract

The crystal and molecular structure of a toxin from the scorpion Centruroides sculpturatus has been solved by standard x-ray crystallographic methods at 3 Å resolution. Subsequently, the 3 Å model has been refined and the resolution has been extended to 1.8 Å using the gradient-curvature method. The final reliability index is 0.17 The structure has two and a half turns of α-helix, a three-strand stretch of antiparallel β-sheet and several β-turns. Three of the four disulfide bridges are found in close interaction with the α-helix and β-sheet structures in what constitutes a very rigid part of the molecule. Examination of available scorpion toxin sequences reveals several sections containing invariant and/or semiinvariant amino acids. Many of these residues are found clustered on a rather large flat surface which is also clearly more hydrophobic than other areas on the molecule. These observations suggest that this surface may play a role in the biological action of scorpion toxins. Secondary structure predictions calculated using the method of Dufton and Hider agree well with the x-ray structure. This is also true for other scorpion toxins and reinforces the idea that scorpion toxins are a family of structurally related proteins.