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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033828-06
Application #
3283904
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1984-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1991-06-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Iowa State University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Ames
State
IA
Country
United States
Zip Code
50011