Mouse urinary proteins

Lehman-McKeeman L., Caudill D., Rodriguez P. and Eddy C. (1998). 2-sec-butyl-4,5-dihydrothiazole is a ligand for mouse urinary protein and rat alpha 2p-globulin physiological and toxicological relevance. Toxicol Appl Pharmacol 149, 32-40. 

No ligand-V2R pair has been identified in mammals. However, the rapidly increasing number of identified molecules activating V2R-expressing VSNs (for example, mouse urinary proteins Chamero et al. 2007), together with the ability to express V2Rs in vitro will surely lead to the identification of V2R-ligand pairs. 

However, unlike small molecule pheromones in terrestrial invertebrates such as moths, many terrestrial mammals may increase the activity of their small molecule pheromones by interaction with carrier proteins. For example, in mice the small volatile molecules are presented as ligands of Mouse Urinary Proteins (MUPs). The MUPs provide a slow release of the volatile signal and the highly variable MUPs may also provide individuality to the signal (Hurst et al., 2001 Beynon and Hurst, this volume Hurst and Beynon, this volume). As far as I know, there are no examples among the invertebrates of combining small molecules with proteins. 

Cavaggioni, A., Findlay, J.B.C. Tirindelli, R. 1990. Ligand binding characteristics of homologous rat and mouse urinary proteins and pyrazine-binding protein of calf Comp. Biochem. Physiol, 96B, 513-520. 

PI. 3.IB Mouse chemosignal complex, ligand + urinary protein location of 2-jeobutyl-4,5-dih yd rot hi azole (DHT) within the binding pocket at the N-terminus (lower) in MUP (from Tirindelli et ai, 1998). 

One of the best-studied carrier molecules is produced as a primary excretory constituent of the adult male mouse, known from its consistent high concentration as the major urinary protein (MUP). The basic 3-D structure of the protein was initially obtained from a monoclinic crystal of recombinant protein (MUP-I), constructed by induction in a bacterial expression system and purified to homogeneity (Kuser, 1990). A wild type version of MUP finally yielded to NMR analysis a clone of the r-isoform (162 residues) was labelled and compared with the crystal-structure (Lucke et al., 1990). Two views of the molecule... 

Held W., Gallagher J.F., Hohman C.M., Kuhn N.J., et al. (1987). Identification and characterization of functional genes encoding the mouse major urinary proteins. Mol Cell Biol 10, 3705-3712. 

Lucke C., Franzoni L., Abbate F., Lohr F., et al. (1999). Solution structure of a recombinant mouse major urinary protein. Eur J Biochem 266, 1210-1218. 

Novotny M., Ma W., Wiesler D. and Zidek L. (1999). Positive identification of the puberty-accelerating pheromone of the house mouse the volatile ligands associating with the major urinary protein. Proc Roy Soc Lond (B) 266, 2017-2022. 

Robertson D., Benyon R.L. and Evershed R. (1993). Extraction, characterization and binding analysis of two pheromonally active ligands associated with major urinary proteins of house mouse (Mus musculus). J Chem Ecol 19, 1405-1416. 

Shaw P., Held W. and Hastie N. (1983). The gene family for major urinary proteins, expression in several secretory tissues of the mouse. Cell 32, 755-761. 

Zidek L., Stone M., Lato S., Pagel M., et al. (1999). NMR-mapping of the recombi mouse major urinary protein-I binding site occupied by the pheromone 2-sec-bi 4,5-dihydrothiazole. Biochem 38, 9850-9861. 

Armstrong, S. D., Robertson, D. H. L., Cheetham, S. A., Hurst, J. L. and Beynon, R. J. (2005) Structural and functional differences in isoforms of mouse major urinary proteins a male-specific protein that preferentially binds a male pheromone. Biochem. J. 391, 343-350. 

Bennett, K. L., Lalley, P. A., Barth, R. K. and Hastie, N. D. (1982) Mapping the structural genes coding for the major urinary proteins in the mouse combined use of recombinant inbred strains and somatic cell hybrids. Proc. Natl. Acad. Sci. USA 79, 1220-4. 

Beynon, R. J. and Hurst, J. L. (2003) Multiple roles of major urinary proteins in the house mouse, Mus domesticus. Biochem. Soc. Trans. 31, 142-6. 

Bishop, J. O., Clark, A. J., Qissold, P. M., Hainey, S. and Francke, U. (1982) Two main groups of mouse major urinary protein genes, both largely located on chromosome 4. EMBO J. 1,615-20. 

Shahan, K., Denaro, M., Gilmartin, M., Shi, Y. and Derman, E. (1987) Expression of six mouse major urinary protein genes in the mammary, parotid,sublingual, submaxillary, and lachrymal glands and in the liver. Mol. Cell. Biol. 7, 1947-1954. 

Timm, D. E., Baker, L. J., Mueller, H., Zidek, L. and Novotny, M. V. (2001) Structural basis of pheromone binding to mouse major urinary protein (MUP-I). Protein Sci. 10, 997-1004. 

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