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Pheromone binding by polymorphic mouse major urinary proteins
Author(s) -
Sharrow Scott D.,
Vaughn Jeffrey L.,
Žídek Lukáš,
Novotny Milos V.,
Stone Martin J.
Publication year - 2002
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.0204202
Subject(s) - gene isoform , isothermal titration calorimetry , dissociation constant , sex pheromone , pheromone , recombinant dna , chemistry , ligand (biochemistry) , microbiology and biotechnology , stereochemistry , biology , biochemistry , receptor , gene , genetics
Mouse major urinary proteins (MUPs) have been proposed to play a role in regulating the release and capture of pheromones. Here, we report affinity measurements of five recombinant urinary MUP isoforms (MUPs‐I, II, VII, VIII, and IX) and one recombinant nasal isoform (MUP‐IV) for each of three pheromonal ligands, (±)‐2‐ sec ‐butyl‐4,5‐dihydrothiazole (SBT), 6‐hydroxy‐6‐methyl‐3‐heptanone (HMH), and (±)dehydro‐ exo ‐brevicomin (DHB). Dissociation constants for all MUP‐pheromone pairs were determined by isothermal titration calorimetry, and data for SBT were corroborated by measurements of intrinsic protein fluorescence. We also report the isolation of MUP‐IV protein from mouse nasal extracts, in which MUP‐IV mRNA has been observed previously. The affinity of each MUP isoform for SBT (K d ∼ 0.04 to 0.9 μM) is higher than that for DHB (K d ∼ 26 to 58 μM), which in turn is higher than that for HMH (K d ∼ 50 to 200 μM). Isoforms I, II, VIII, and IX show very similar affinities for each of the ligands. MUP‐VII has approximately twofold higher affinity for SBT but approximately twofold lower affinity for the other pheromones, whereas MUP‐IV has ∼23‐fold higher affinity for SBT and approximately fourfold lower affinity for the other pheromones. The variations in ligand affinities of the MUP isoforms are consistent with structural differences in the binding cavities of the isoforms. The data indicate that the concentrations of available pheromones in urine may be influenced by changes in the expression levels of urinary MUPs or the excretion levels of other MUP ligands. The variation in pheromone affinities of the urinary MUP isoforms provides only limited support for the proposal that MUP heterogeneity plays a role in regulating profiles of available pheromones. However, the binding data support the proposed role of nasal MUPs in sequestering pheromones and possibly transporting them to their receptors.