BBMB Research Seminars

September 13, 2007
Don Dean
Department of Biochemistry, Molecular Genetics & Entomology
Ohio State University
"Molecular Design of Mosquitocidal Proteinsy"
1414 Molecular Biology Buidling
4:10 p.m.

Abstract:

The insecticidal Bacillus thuringiensis crystal proteins (Cry toxins) are, for the most part, selective in their action. In other words, a particular toxin is active on a small set of insects. Many show selectivity to just a few species in a particular genus. A few, however are active on selected insects across two or more orders of insects. Nature has selected these specificities by evolving surface residues of some predecessor scaffolding protein to recognize and bind to insect midgut proteins, which function as receptors. Through a much shorter period of time (albeit 25 years) we have learned which surface residues of different Cry toxins are active in receptor binding of different insects. This has allowed us to manipulate these to change the specificity of Cry toxins. As an example, Cry1Aa is normally selectively active to a few caterpillar larvae. Through rational design and luck, toxicity to the mosquito Culex pipiens was introduced by selected deletions and substitutions of the loop residues of domain II. Toxicity to its natural target Manduca sexta was concomitantly abolished. Further refinement has increased the toxicity to Culex and added toxicity to the mosquito Aedes. The successful grafting of the alternate mosquito toxicity onto the original lepidopteran Cry1Aa toxin demonstrates the possibility of designing and engineering a desired toxicity into any toxin of a common scaffold by reshaping the receptor binding region with desired specificities.