The objective is to determine the three-dimensional structures of a set of protein neurotoxins that interact with sodium channels of excitable membranes. The structures will be determined using the techniques of protein crystallography. Major emphasis will be placed on structure-function studies of protein neurotoxins from the scorpion, Centruroides sculpturatus Ewing, including toxins that affect the inactivation of sodium channels as well as ones that alter activation kinetics. These studies will include high-resolution refinements of the variant-3 toxin; refinement of two crystalline forms of the variant-2 toxin; determination of the structure of Toxin V; and crystallographic studies of toxins III and IV. The results of these studies will be used to better understand the mechanisms by which scorpion neurotoxins affect sodium channels; the structural features that may account for the different effects that these purified toxins exert on activation and inactivation kinetics; structural features that may account for large differences in the toxicities of individual toxins; and structural factors that may eventually help account for differences in species specificity displayed by scorpion toxins. The crystallographic studies will be extended to include sea anemone neurotoxins, which are small proteins that compete for scorpion toxin binding sites. Comparisons of scorpion toxin and sea anemone toxin structures should be of value in identifying those structural features that may account for the neurotoxic activities of these proteins.
| Zhao, B; Carson, M; Ealick, S E et al. (1992) Structure of scorpion toxin variant-3 at 1.2 A resolution. J Mol Biol 227:239-52 |
