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High resolution X-ray structures of mouse major urinary protein nasal isoform in complex with pheromones.
- Source :
-
Protein science : a publication of the Protein Society [Protein Sci] 2010 Aug; Vol. 19 (8), pp. 1469-79. - Publication Year :
- 2010
-
Abstract
- In mice, the major urinary proteins (MUP) play a key role in pheromonal communication by binding and transporting semiochemicals. MUP-IV is the only isoform known to be expressed in the vomeronasal mucosa. In comparison with the MUP isoforms that are abundantly excreted in the urine, MUP-IV is highly specific for the male mouse pheromone 2-sec-butyl-4,5-dihydrothiazole (SBT). To examine the structural basis of this ligand preference, we determined the X-ray crystal structure of MUP-IV bound to three mouse pheromones: SBT, 2,5-dimethylpyrazine, and 2-heptanone. We also obtained the structure of MUP-IV with 2-ethylhexanol bound in the cavity. These four structures show that relative to the major excreted MUP isoforms, three amino acid substitutions within the binding calyx impact ligand coordination. The F103 for A along with F54 for L result in a smaller cavity, potentially creating a more closely packed environment for the ligand. The E118 for G substitution introduces a charged group into a hydrophobic environment. The sidechain of E118 is observed to hydrogen bond to polar groups on all four ligands with nearly the same geometry as seen for the water-mediated hydrogen bond network in the MUP-I and MUP-II crystal structures. These differences in cavity size and interactions between the protein and ligand are likely to contribute to the observed specificity of MUP-IV.
- Subjects :
- Amino Acid Sequence
Animals
Carrier Proteins genetics
Carrier Proteins metabolism
Ligands
Male
Mice
Models, Molecular
Molecular Sequence Data
Molecular Structure
Nose anatomy & histology
Pheromones genetics
Pheromones metabolism
Protein Binding
Protein Isoforms genetics
Protein Isoforms metabolism
Proteins genetics
Proteins metabolism
Thermodynamics
Carrier Proteins chemistry
Nasal Mucosa metabolism
Pheromones chemistry
Protein Isoforms chemistry
Protein Structure, Tertiary
Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1469-896X
- Volume :
- 19
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Protein science : a publication of the Protein Society
- Publication Type :
- Academic Journal
- Accession number :
- 20509168
- Full Text :
- https://doi.org/10.1002/pro.426