Bombyx mori pheromone-binding protein binding nonpheromone ligands: implications for pheromone recognition.

Area of Science:

• Structural biology
• Insect chemical ecology
• Molecular mechanisms of olfaction

Background:

• Insect pheromone-binding proteins (PBPs) are essential for olfaction, transporting hydrophobic pheromones through the aqueous sensillar lymph to G protein-coupled receptors (GPCRs).
• The PBP-GPCR system exhibits high ligand specificity, crucial for successful mating behavior.
• Disentangling the discriminatory roles of PBPs versus GPCRs has been challenging.

Purpose of the Study:

• To elucidate the structural basis of ligand binding and discrimination by insect pheromone-binding proteins.
• To investigate the plasticity of the PBP binding site when interacting with different odorants.
• To assess the potential role of PBPs as filters in pheromone signal processing.

Main Methods:

• X-ray crystallography and Nuclear Magnetic Resonance (NMR) spectroscopy were employed to determine the three-dimensional structures of a Bombyx mori PBP.
• Structures were determined for the PBP in complex with its cognate ligand (bombykol), a synthetic ligand (iodohexadecane), and a non-pheromone odorant (bell pepper odorant).

Main Results:

• The crystal structure of the Bombyx mori PBP complexed with iodohexadecane was determined at 1.9 Å resolution.
• The crystal structure of the Bombyx mori PBP complexed with bell pepper odorant was determined at 2.0 Å resolution.
• These structures revealed significant conformational flexibility within the PBP ligand-binding pocket, accommodating structurally diverse molecules.

Conclusions:

• The ligand-binding site of insect pheromone-binding proteins demonstrates remarkable plasticity.
• Despite this flexibility, PBPs likely function as initial filters, contributing to the overall specificity of pheromone detection.
• Structural insights into PBP-ligand interactions provide a foundation for understanding olfactory discrimination in insects.