Structural basis of pheromone binding to mouse major urinary protein (MUP‐I)

The mouse major urinary proteins are pheromone‐binding proteins that function as carriers of volatile effectors of mouse physiology and behavior. Crystal structures of recombinant mouse major urinary protein‐I (MUP‐I) complexed with the synthetic pheromones, 2‐sec‐butyl‐4,5‐dihydrothiazole and 6‐hydroxy‐6‐methyl‐3‐heptanone, have been determined at high resolution. The purification of MUP‐I from mouse liver and a high‐resolution structure of the natural isolate are also reported. These results show the binding of 6‐hydroxy‐6‐methyl‐3‐heptanone to MUP‐I, unambiguously define ligand orientations for two pheromones within the MUP‐I binding site, and suggest how different chemical classes of pheromones can be accommodated within the MUP‐I β‐barrel.

[1]  F. Bronson,et al.  Estrus-Inducing Pheromone of Male Mice: Transport by Movement of Air , 1968, Science.

[2]  T A Jones,et al.  Crystallographic refinement of human serum retinol binding protein at 2Å resolution , 1990, Proteins.

[3]  A D Ellington,et al.  NMR mapping of the recombinant mouse major urinary protein I binding site occupied by the pheromone 2-sec-butyl-4,5-dihydrothiazole. , 1999, Biochemistry.

[4]  C. Jones,et al.  Sexual dimorphism and growth hormone regulation of a hybrid gene in transgenic mice. , 1992, Molecular endocrinology.

[5]  Darren R. Flower,et al.  Bovine β-lactoglobulin at 1.8 Å resolution — still an enigmatic lipocalin , 1997 .

[6]  T. Roderick,et al.  Genes that modify expression of major urinary proteins in mice , 1988, Molecular and cellular biology.

[7]  F. Löhr,et al.  Solution structure of a recombinant mouse major urinary protein. , 1999, European journal of biochemistry.

[8]  J. Zou,et al.  Improved methods for building protein models in electron density maps and the location of errors in these models. , 1991, Acta crystallographica. Section A, Foundations of crystallography.

[9]  C. Mucignat-Caretta,et al.  Acceleration of puberty onset in female mice by male urinary proteins. , 1995, The Journal of physiology.

[10]  Milos V. Novotny,et al.  Increased protein backbone conformational entropy upon hydrophobic ligand binding , 1999, Nature Structural Biology.

[11]  A. North,et al.  Pheromone binding to two rodent urinary proteins revealed by X-ray crystallography , 1992, Nature.

[12]  M. Novotny,et al.  A unique urinary constituent, 6-hydroxy-6-methyl-3-heptanone, is a pheromone that accelerates puberty in female mice. , 1999, Chemistry & biology.

[13]  U. Francke,et al.  Two main groups of mouse major urinary protein genes, both largely located on chromosome 4. , 1982, The EMBO journal.

[14]  A. North,et al.  Crystallization of and preliminary X-ray data for the mouse major urinary protein and rat α-2u globulin☆ , 1991 .

[15]  A. Bergman,et al.  A methylsulphonyl metabolite of a polychlorinated biphenyl can serve as a ligand for alpha 2mu-globulin in rat and major-urinary-protein in mice. , 1990, Xenobiotica; the fate of foreign compounds in biological systems.

[16]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[17]  C. Mucignat-Caretta,et al.  Major urinary proteins, α2U-globulins and aphrodisin , 2000 .

[18]  M. Potter,et al.  Major Urinary Protein Complex of Normal Mice: Origin , 1965, Science.

[19]  Collaborative Computational,et al.  The CCP4 suite: programs for protein crystallography. , 1994, Acta crystallographica. Section D, Biological crystallography.

[20]  D R Flower,et al.  The lipocalin protein family: structure and function. , 1996, The Biochemical journal.

[21]  R. Huber,et al.  Molecular structure of the bilin binding protein (BBP) from Pieris brassicae after refinement at 2.0 A resolution. , 1987, Journal of molecular biology.

[22]  M. Novotny,et al.  Positive identification of the puberty-accelerating pheromone of the house mouse: the volatile ligands associating with the major urinary protein , 1999, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[23]  Z. Otwinowski,et al.  [20] Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[24]  A. Holmgren,et al.  Protein disulfide-isomerase is a substrate for thioredoxin reductase and has thioredoxin-like activity. , 1990, The Journal of biological chemistry.

[25]  H. M. Marsden,et al.  Estrous Synchrony in Mice: Alteration by Exposure to Male Urine , 1964, Science.

[26]  D R Flower,et al.  Bovine beta-lactoglobulin at 1.8 A resolution--still an enigmatic lipocalin. , 1997, Structure.

[27]  G J Kleywegt,et al.  The structures of alpha 2u-globulin and its complex with a hyaline droplet inducer. , 1999, Acta crystallographica. Section D, Biological crystallography.

[28]  M. Novotny,et al.  Adrenal-mediated endogenous metabolites inhibit puberty in female mice. , 1986, Science.

[29]  M. Novotny,et al.  Promotion of the Whitten effect in female mice by synthetic analogs of male urinary constituents. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[30]  M. Novotny,et al.  Synthetic pheromones that promote inter-male aggression in mice. , 1985, Proceedings of the National Academy of Sciences of the United States of America.