Vip3 insecticidal proteins: Structure and mode of action

Modern agriculture makes use of bacterial genes to protect crops from the attack of insects. Bt-crops are commercialized and express cry and vip3Aa genes from Bacillus thuringiensis, which confer protection against insect pests. Vip3A proteins are highly active against lepidopterans and the fact that they do not share binding sites with Cry proteins makes them perfect “partners” to be combined in insect-protected crops. The structure of Vip3Aa is composed of five well differentiated domains, and in solution the protein spontaneously forms a pyramid-shaped tetramer protoxin. The N-terminal domains of the protein (Domains I and II) are very conserved, mainly formed by α-helices, and are critical for the formation and maintenance of the tetrameric structure. The C-terminal domains (Domains III, IV and V) are highly variable, mainly consisting of β-sheets and thought of being responsible for binding to specific receptors (Domain III) and to glycosylated molecules (Domains IV and V). The activation of the protoxin involves a profound conformational change in which Domains I are reorganized forming a coiled-coil structure that resembles a long “needle”. The tip of this needle inserts into the epithelial membrane eventually causing cell death. To date, no resistance to Vip3Aa proteins has been reported in the field, though laboratory selection and F2 screens have succeeded in obtaining resistant colonies. In contrast to resistance to Cry proteins, no case of alteration of the binding sites has been found in Vip3-resistant insects so far.