Structural and Functional Characterization of Allatostatin Receptor Type-C of Thaumetopoea pityocampa, a Potential Target for Next-Generation Pest Control Agents

Insect neuropeptide receptors, including allatostatin receptor type C (AstR-C), a G protein-coupled receptor, are among the potential targets for designing next-generation pesticides that despite their importance in offering a new mode-of-action have been overlooked. Focusing on AstR-C of Thaumetopoea pityocampa, a common pest in Mediterranean countries, by employing resonance energy transfer-based methods, we showed G alpha i/o coupling and beta-arrestin recruitment of the receptor at sub-nanomolar and nanomolar ranges of the endogenous ligand, AST-C, respectively. Molecular docking and molecular dynamics simulation studies revealed the importance of extracellular loop 2 in AstRC/AST-C interaction, and a combination of in silico and in vitro approaches showed the substantial role of Q271(6.55) in G protein-dependent activation of AstR-C possibly via contributing to the flexibility of the receptor's structure. The functional and structural insights obtained on T. pit AstR-C positively assist future efforts in developing environmentally friendly pest control agents that are needed urgently.