Bacillus and Lysinibacillus bacteria naturally produce a variety of pesticidal proteins tailored to specific target insects. These proteins include pore-forming proteins that bind to the midgut region of insects and create perforations in these tissues, ultimately leading to septicemia and the death of the insect targets. These properties make them promising candidates for use as biopesticides in insect pest management. The specificity of these proteins is determined by their ability to recognize receptors present on the surface of target cells. However, the intricate molecular mechanisms governing the interactions between toxins and receptors for these proteins remain unresolved.
One such pesticidal protein is the Tpp1/2 (formerly known as BinAB) binary pesticidal protein from Lysinibacillus sphaericus, which exhibits selective activity against Culex and Anopheles mosquitoes. This protein system has been widely employed on a global scale to control mosquito populations responsible for disease transmission. The receptor protein, an alpha-glucosidase, has been identified as the receptor for Tpp2. It is believed that Tpp2 facilitates the internalization of the Tpp1 (BinA) component, which is responsible for pore formation and cell killing.
In this study, we employ a combination of cryo-EM, mass photometry and protein mutagenesis techniques to investigate the interaction between Tpp2Aa2 and its receptor protein, Cqm1, found in Culex quinquefasciatus mosquitoes. This research aims to advance our understanding of pesticidal protein specificity, which is crucial for the safety and commercial viability of these toxins. Furthermore, this work will pave the way for studies aimed at improving the effectiveness and stability of pore-forming proteins for targeting pests and expanding their applicability to a broader range of target insects. Ultimately, our goal is to develop more effective and environmentally friendly insecticides for pest control.