title: Pheromone discrimination by a pH-tuned polymorphism of the Bombyx mori pheromone-binding protein.
abstract: The Bombyx mori pheromone-binding protein (BmorPBP) is known to adopt two different conformations. These are BmorPBP(A), where a regular helix formed by the C-terminal dodecapeptide segment, α7, occupies the ligand-binding cavity, and BmorPBP(B), where the binding site is free to accept ligands. NMR spectra of delipidated BmorPBP solutions at the physiological pH of the bulk sensillum lymph near pH 6.5 show only BmorPBP(A), and in mixtures, the two species are in slow exchange on the chemical shift frequency scale. This equilibrium has been monitored at variable pH and ligand concentrations, demonstrating that it is an intrinsic property of BmorPBP that is strongly affected by pH variation and ligand binding. This polymorphism tunes BmorPBP for optimal selective pheromone transport: Competition between α7 and lipophilic ligands for its binding cavity enables selective uptake of bombykol at the pore endings in the sensillum wall, whereas compounds with lower binding affinity can only be bound in the bulk sensillum lymph. After transport across the bulk sensillum lymph into the lower pH area near the dendritic membrane surface, bombykol is ejected near the receptor, whereas compounds with lower binding affinity are ejected before reaching the olfactory receptor, rendering them susceptible to degradation by enzymes present in the sensillum lymph.
authors.affiliation: Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule Zürich, CH-8093 Zurich, Switzerland.
authors.forename: Fred F
authors.initials: FF
authors.lastname: Damberger
authors.forename: Erich
authors.initials: E
authors.lastname: Michel
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishida
authors.forename: Walter S
authors.initials: WS
authors.lastname: Leal
authors.forename: Kurt
authors.initials: K
authors.lastname: Wüthrich
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D012831:Bombyx / Q000378:metabolism* / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005233:Fatty Alcohols / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010675:Pheromones / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics; D011487:Protein Conformation; D012903:Smell / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D005233:Fatty Alcohols; D019476:Insect Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010675:Pheromones; C403094:pheromone-binding protein, Bombyx; C006787:bombykol
keywords: NMR structure; amide proton exchange; conformational equilibrium; insect odorant-binding protein; selective transport of pheromones