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Pheromone binding to two rodent urinary proteins revealed by X-ray crystallography

Abstract

THE principal protein excreted in male rat urine, urinary α2-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 α2-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 α2-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 Å resolution) and rat urinary α2-globulin (at 2.8 Å resolution). The results corroborate the role of these proteins in pheromone transport and elaborate the structural basis of ligand binding.

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References

  1. Cowley, J. J. Biological Determinants of Sexual Behaviour (ed. Hutchinson, J. B.) 87–125 (Wiley. Chichester, 1978).

    Google Scholar 

  2. Cavaggioni, A., Sorbi, R. T., Keen, J. N., Pappin, D. J. C. & Findlay, J. B. C. FEBS Lett. 212, 225–228 (1987).

    Article  CAS  Google Scholar 

  3. Borghoff, S. J., Short, B. G. & Swenberg, J. A. Rev. Pharmac. Toxicol. 30, 349–367 (1990).

    Article  CAS  Google Scholar 

  4. Flower, D. R., North, A. C. T. & Attwood, T. K. Biochim. biophys. Res. Commun. 180, 69–74 (1991).

    Article  CAS  Google Scholar 

  5. Tirindelli, R., Keen, J. N., Cavaggioni, A., Eliopoulos, E. E. & Findlay, J. B. C. Eur. J. Biochem. 185, 569–572 (1989).

    Article  CAS  Google Scholar 

  6. Sivaprasadarao, A. & Findlay, J. B. C. Biochem. J. 255, 561–569 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Böcskei, Z. et al. J. molec. Biol. 218, 699–701 (1991).

    Article  Google Scholar 

  8. Bacchini, A., Gaetani, E. & Cavaggioni, A. Experimentia (in the press).

  9. Cavaggioni, A., Findlay, J. B. C. & Tirindelli, R. Comp. Biochem. Physiol. 96b, 513–520 (1990).

    CAS  Google Scholar 

  10. Kimura, H. et al. J. biol Chem. 266, 5963–5972 (1991).

    CAS  PubMed  Google Scholar 

  11. Kabsch, W. J. appl. Crystallogr. 21, 67–71 (1988).

    Article  CAS  Google Scholar 

  12. Wang, B. C. Meth. Enzym. 115, 90–112 (1985).

    Article  CAS  Google Scholar 

  13. Cherfils, J. & Dumas, C. J. appl. Crystallogr. 21, 985–987 (1988).

    Article  Google Scholar 

  14. Brunger, A. T., Kuriyan, J. & Karplus, M. Science 235, 458–460 (1987).

    Article  ADS  CAS  Google Scholar 

  15. Hendrickson, W. A. Meth. Enzym. 115, 252–270 (1985).

    Article  CAS  Google Scholar 

  16. Fitzgerald, P. M. D. J. appl. Crystallogr 21, 273–288 (1988).

    Article  CAS  Google Scholar 

  17. Jones, T. A. Meth. Enzym. 115, 157–171 (1985).

    Article  CAS  Google Scholar 

  18. Cowan, S. W., Newcomer, M. E. & Jones, T. A. Proteins 8, 44–61 (1990).

    Article  CAS  Google Scholar 

  19. Papiz, M. A. et al. Nature 324, 383–385 (1986).

    Article  ADS  CAS  Google Scholar 

  20. Clark, A. J., Ghazal, P., Bingham, R. W., Barrett, P. & Bishop, J. O. EMBO J. 4, 3159–3159 (1985).

    Article  CAS  Google Scholar 

  21. Clark, A. J., Clissold, P. M., Shawi, R. A., Beattie, P. & Bishop, J. O. EMBO J. 3, 1045–1052 (1984).

    Article  CAS  Google Scholar 

  22. Ichiyoshi, Y., Endo, H. & Yamamoto, M. Biochim biophys. Acta 910, 43–51 (1987).

    Article  CAS  Google Scholar 

  23. Parry-Smith, D. J. & Attwood, T. K. CABIOS 7, 233–235 (1991).

    CAS  PubMed  Google Scholar 

  24. North, A. C. T. Biochem. Soc. Symp. 57, 35–48 (1991).

    Google Scholar 

  25. Holden, H. M., Rypniewsky, W. R., Law, J. H. & Rayment, I. EMBO J. 6, 1565–1570 (1987).

    Article  CAS  Google Scholar 

  26. Huber, R. et al. J. molec. Biol. 195, 423–434 (1987).

    Article  CAS  Google Scholar 

  27. Flower, D. R. J. molec. Graph 9, 257–258 (1991).

    Article  CAS  Google Scholar 

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Böcskei, Z., Groom, C., Flower, D. et al. Pheromone binding to two rodent urinary proteins revealed by X-ray crystallography. Nature 360, 186–188 (1992). https://doi.org/10.1038/360186a0

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