Molecular architecture and activation of the insecticidal protein Vip3Aa from Bacillus thuringiensis

Bacillus thuringiensis Vip3 (Vegetative Insecticidal Protein 3) toxins are widely used in biotech crops to control Lepidopteran pests. These proteins are produced as inactive protoxins that need to be activated by midgut proteases to trigger cell death. However, little is known about their three-dimensional organization and activation mechanism at the molecular level. Here, we have determined the structures of the protoxin and the protease-activated state of Vip3Aa at 2.9 Å using cryo-electron microscopy. The reconstructions show that the protoxin assembles into a pyramid-shaped tetramer with the C-terminal domains exposed to the solvent and the N-terminal region folded into a spring-loaded apex that, after protease activation, drastically remodels into an extended needle by a mechanism akin to that of influenza haemagglutinin. These results provide the molecular basis for Vip3 activation and function, and serves as a strong foundation for the development of more efficient insecticidal proteins

Lysinibacillus sphaericus

Lysinibacillus sphaericus (Ls) strains that produce insecticidal proteins show high activity against mosquito larvae. The most active of these is the binary (Bin) toxin that acts following ingestion and, after midgut processing and binding to specific receptors, provokes cytopathological effects and leads to larval death. Bin toxin displays specific action against some species of medical importance (e.g. Culex and Anopheles) and it is safe to non-target organisms. These features have led to the production of biolarvicides based on this bacterium and its effectiveness to control mosquito larvae has been widely related in the literature. The field utilisation of Ls has also shown that resistance could be selected among exposed populations and the mechanisms and genes involved in this process have been described. Management strategies can be successfully employed to avoid resistance and Ls can be used within integrated programmes as a selective and efficient agent to control mosquitoes