PHEROMONE BINDING TO 2 RODENT URINARY PROTEINS REVEALED BY X-RAY CRYSTALLOGRAPHY

THE principal protein excreted in male rat urine, urinary alpha2-globulin and the homologous mouse protein, major urinary protein, have been well characterized, although their functions remain unclear. Male rat urine affects the behaviour and sexual response of female rats1, leading to the proposal that rodent urinary proteins are responsible for binding pheromones and their subsequent release from drying urine2. Urinary alpha2-globulin is also involved in hyaline droplet nephropathy, an important toxicological syndrome in male rats resulting from exposure to a number of industrial chemicals and characterized by the accumulation of liganded urinary alpha2-globulin in lysosomes in the kidney, followed by the induction of renal cancer3. We now report the three-dimensional structures of mouse major urinary protein (at 2.4 angstrom resolution) and rat urinary alpha2-globulin (at 2.8 angstrom resolution). The results corroborate the role of these proteins in pheromone transport and elaborate the structural basis of ligand binding.