Major urinary protein structure

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... 

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. 

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. 

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. 

Beynon RJ, Hurst JL, Gaskell SJ, Hubbard SJ, Humphries RE, Malone N, Marie AD, Martinsen L, Nevison CM, Payne CE, Robertson DHL, Veggerby C (2001) Mice MUPs and myths structure-function relationships of the major urinary proteins. In March-lewska-Koj A, Lepri JJ, Muller-Schwarze D (eds) Chemical signals in vertebrates IX. Cluver/Plenum, New York, p 149... 

Rat a2-gIobulin (A2U) and the homologous mouse protein (major urinary protein, MUP) are the principal proteins secreted in the urine of male rodents. Because male urine affects the behavior and sexual response of females, it has been suggested that these proteins function as pheromone-binding proteins. The crystal structures of both proteins have been determined (Bocskei et al., 1992). As expected (Cowan et al, 1990), both structures have the RBP fold. The Ca coordinates of the /3 barrel agree with an RMS difference of approximately 1.2 A. Both contain a ligand in the center of the barrel, where extensive interactions are made with the hydrophobic residues lining the barrel. For the MUP... 

Clark, A. J., Ghazal, P., Bingham, R. W., Barrett, D., and Bishop, J. O., 1985, Sequence structures of a mouse major urinary protein gene and pseudogene compared, 4 3159-3165. 

Not only is the structure of the sex pheromone identical in both moths and Asian elephants and its function similar, but the study of protein carriers promises to be equally fascinating. The delineation of postulated protein carriers for this acetate has the potential to provide similar evolutionary information about lipocalin-like urinary proteins and pheromone binding proteins. Insect pheromone binding proteins that bind Z7—12 Ac have a different amino acid composition and two-dimensional structure than vertebrate odorant binding proteins so far described, including major urinary proteins (Robertson, Cox, Gaskell, Evershed Beynon, 1996 Steinbrecht, 1996 Pelosi, 1994). 

Figure 3. Three-dimensional structure of the major urinary protein from the house mouse. The three dimensional structure of this protein has been solved by X-ray crystallography. In this representation of the protein, the central barrel-like calyx has been cut away to expose the volume and shape of the central cavity. The bubble-like surface therefore encloses this cavity.

Fig. 2.18 Tertiary structure of a mouse major urinary protein. (From http //en.wikipedia.org/wild/Major urinaryjproteins).

Mains MO, Braselton WE. 1983. Protein binding and structure identification of the major urinary metabolite of 4,4 -methylenebis-2-chloroaniline in dogs. In 67th Annual Meeting of the Federation of American Societies for Experimental Biology, Chicago, IL, April 10-15, 1983. Fed Proc 42(3) Abstract 354. 

A major advance was made by Edelman and Gaily (6) who showed that Bence Jones proteins are L chains, identical in structure to L chains of the serum myeloma protein of the same patient (in those patients who manifest both types of protein). The presence of a urinary protein in association with multiple myeloma had been reported by Henry Bence Jones in 1847 (7). Such proteins have the interesting property of precipitating when the urine is heated to 50°-60°C, redissolving at 100°, and reprecipitating upon cooling. The criteria used by Gaily and Edelman to relate the Bence Jones protein and myeloma L chain included the amino acid composition and the mobility of the protein bands upon electrophoresis in starch gel. 

Urinary casts, often excreted by patients having renal disease, possess414 antigenic determinants in common with the Tamm-Horsfall protein (see p. 414), and, indeed, this glycoprotein is the major component of the casts.414-416 However, the reason for its aggregation is as yet unknown. Other pathological states may well be found to be associated with abnormalities in the structure or metabolism, or both, of glycoproteins. 

A growing number of clinical studies have demonstrated that fluorescence spectroscopy can be used to distinguish normal and abnormal human tissues in vivo in the skin, head and neck, genito-urinary tract, gastrointestinal tract, breast and brain. It is well known that fluorescence intensity and lineshape are a function of both the excitation and emission wavelength in samples containing multiple chromophores, such as human tissue. Major fluorescence contributors are structural proteins, NADH, FAD, tryptophane and porphyrins. 

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