title: Comparative study of the molecular variation between 'central' and 'peripheral' MUPs and significance for behavioural signalling.
abstract: MUPs (major urinary proteins) play an important role in chemical signalling in rodents and possibly other animals. In the house mouse (Mus musculus domesticus) MUPs in urine and other bodily fluids trigger a range of behavioural responses that are only partially understood. There are at least 21 Mup genes in the C57BL/6 mouse genome, all located on chromosome 4, encoding sequences of high similarity. Further analysis separates the MUPs into two groups, the 'central' near-identical MUPs with over 97% sequence identity and the 'peripheral' MUPs with a greater degree of heterogeneity and approximately 20-30% non-conserved amino acids. This review focuses on differences between the two MUP sub-groups and categorizes these changes in terms of molecular structure and pheromone binding. As small differences in amino acid sequence can result in marked changes in behavioural response to the signal, we explore the potential of single amino acid changes to affect chemical signalling and protein stabilization. Using analysis of existing molecular structures available in the PDB we compare the chemical and physical properties of the ligand cavities between the MUPs. Furthermore, we identify differences on the solvent exposed surfaces of the proteins, which are characteristic of protein-protein interaction sites. Correlations can be seen between molecular heterogeneity and the specialized roles attributed to some MUPs.
authors.affiliation: *NMR Centre for Structural Biology, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, U.K.
authors.forename: Marie M
authors.initials: MM
authors.lastname: Phelan
authors.affiliation: †Protein Function Group, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, U.K.
authors.forename: Lynn
authors.initials: L
authors.lastname: McLean
authors.affiliation: ‡Mammalian Behaviour and Evolution Group, Institute of Integrative Biology, University of Liverpool, Leahurst Campus, Neston CH64 7TE, U.K.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Hurst
authors.affiliation: †Protein Function Group, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, U.K.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Beynon
authors.affiliation: *NMR Centre for Structural Biology, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, U.K.
authors.forename: Lu-Yun
authors.initials: LY
authors.lastname: Lian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010675:Pheromones / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C555029:Mup20 protein, mouse; D010675:Pheromones; D011506:Proteins; C035737:major urinary proteins