The focus of research is the determination of the three dimensional structure of cytolytic toxins and an understanding of the relationship of their structure to biochemical mechanisms of toxicity. Detailed knowledge of the structure of cytolytic toxins will contribute ultimately to a better understanding of the mechanisms of protein-membrane interactions. New methods of drug transport may result from a basic knowledge of protein interactions with cell membranes. In addition, the basic research may lead to improvements in a new generation of pesticides which are nontoxic to mammalian species. Crystals of cytolytic toxin (cytolysin A-III, Mr=17,000) from the sea anemone Stoichactis helianthus grow under three conditions. Structure determinations of the toxin in different crystal environments shall provide a molecular model for the protein, as well as provide a basis for modeling the structure of the transmembrane channel formed by the toxin. The initial model of the toxin will result from techniques of X-ray diffraction, computer modeling and refinement of a molecular model against X-ray diffraction data. In concert with research on the structure of the cytolysin A-III, we shall search for conditions of crystal growth for the Delta-endotoxin of Bacillus thuringiensis. Three forms of the Delta-endotoxin will be available for investigation. Growth of the crystals of the Delta-endotoxin will lead ultimately to a long term study of the relationship of structure to membrane specificity of this important family of toxins.
