Structural basis of pore formation by mosquito-larvicidal proteins from bacillus thuringiensis

Abstract

The insecticidal character of the three-domain Cry 􀀃-endotoxins produced by Bacillus thuringiensis during sporulation is believed to be caused by their capability to generate lytic pores in the target larval midgut cell membranes. This review describes toxic mechanisms with emphasis on the structural basis of pore formation by two closely related dipteran-specific toxins, Cry4Aa and Cry4Ba, which are highly toxic to mosquito larvae. One proposed toxic mechanism via an “umbrella-like” structure involves membrane penetration and pore formation by the 􀀁4-􀀁5 transmembrane hairpin. The lipid-induced 􀀂-conformation of 􀀁7 could possibly serve as a lipid anchor required for an efficient insertion of the pore-forming hairpin into the bilayer membrane. Though current electron crystallographic data are still inadequate to provide such critical insights into the structural details of the Cry toxin-induced pore architecture, this pivotal evidence clearly reveals that the 65-kDa active toxin in association with the lipid membrane could exist in at least two different trimeric conformations, implying the closed and open states of a functional pore.