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Pheromone binding by polymorphic mouse major urinary proteins

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SHARROW Scott D. VAUGHN Jeffrey L. ŽÍDEK Lukáš NOVOTNY Milos V. STONE Martin J

Rok publikování 2002
Druh Článek v odborném periodiku
Časopis / Zdroj Protein Science
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Obor Biochemie
Klíčová slova Binding affinity; isothermal titration calorimetry; major urinary proteins eins; pheromones; selectivity
Popis Mouse major urinary proteins (MUPs) have been proposed to play a role in regulat ing 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 on e 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), a nd (+/-)dehydro-exo-brevicomin (DHB). Dissociation constants for all MUP-pherom one pairs were determined by isothermal titration calorimetry, and data for SBT were corroborated by measurements of intrinsic protein fluorescence. We also rep ort the isolation of MUP-IV protein from mouse nasal extracts, in which MUP-IV m RNA has been observed previously. The affinity of each MUP isoform for SBT (Kd ~ 0.04 to 0.9 uM) is higher than that for DHB (Kd ~ 26 to 58 uM), which in turn is higher than that for HMH (Kd ~ 50 to 200 uM). Isoforms I, II, VIII, a nd IX show very similar affinities for each of the ligands. MUP-VII has approxim ately twofold higher affinity for SBT but approximately twofold lower affinity f or 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 differen The data indicate that the concentr ations of available pheromones in urine may be influenced by changes in the expr ession levels of urinary MUPs or the excretion levels of other MUP ligands. The variation in pheromone affinities of the urinary MUP isoforms provides only limi ted support for the proposal that MUP heterogeneity plays a role in regulating p rofiles of available pheromones. However, the binding data support the proposed role of nasal MUPs in sequestering pheromones and possibly transporting them to their receptors. ces in the binding cavities of the isoforms.
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