Architecture et Fonction des Macromolécules Biologiques, URA 9039, CNRS, IFR1, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
Perireceptor transport proteins are small soluble proteins (15-20 kDa) which bind odourants or pheromones, usually hydrophobic molecules. They ferry them to the receptors, through the aqueous compartment which surrounds the olfactory neurones, the nasal mucosa in mammals, the sensillar lymph in insect antennae. In mammals, these proteins fall into the lipocalin family. Our understanding of insect PBPs has even less well developed. No 3D structure has yet been elucidated yet. We have undertaken structure/function studies of these molecules using X-ray diffraction and NMR (Collaboration with R. Ramoni, Parma, and P. Nagnan, INRA-Versailles). Bovine OBP (OBPb) is a homodimer of 2 x159 amino acids, secreted in millimolar concentration by the nasal respiratory epithelium. We have solved the structure of OBPb at 2.0 Å. The protein has the typical fold of a lipocalin but with one startling difference: the single helix of one monomer interacts with the ß barrel of the other, thus displaying the so-called 'domain-swapping'. Two closed cavities are present in the structure, one per monomer, which are filled with endogenous molecules. Their nature has been determined recently by mass spectroscopy and high resolution X-ray structure (1.4 Å resolution) Porcine OBP (OBPp) has a classical lipocalin fold and does not exhibit domain swapping. In contrast with OBPb, the closed internal cavity is devoid of natural ligand. The structures of several complexes of OBPp with various odorants pertaining to diverse chemical classes have been solved at high resolution. The odor molecules are in general poorly defined considering the resolution. The combining site remains basically unchanged between the free and complexed forms. Contacts between the odors and OBPp are mainly hydrophobic. All these features correlate well with average dissociation constants in the millimolar range and with the broad specificity of OBPs.