Vitamin A is an essential nutrient required for growth, reproduction, differentiation of epithelial tissues and vision. The mechanism by which dietary retinoids are absorbed and converted to various metabolites is complex. Specific retinoid binding proteins have been implicated in mediating the absorption, intracellular trafficking and the action of vitamin A. In particular, we are interested in the role of cellular retinol binding protein II (CRBP II), which is present exclusively in the small intestine in the adult animal, suggesting that it is uniquely adapted to the intestinal absorption and metabolism of retinol. CRBP II is closely homologous to cellular retinol binding protein (CRBP), which in contrast to CRBP II, is found in many epithelial tissues. Monospecific ligands that bind to only one protein, would be extremely useful for dissecting the metabolic roles of the retinoid binding proteins, and could potentially lead to the design of new drugs. To identify or design such ligands requires further understanding of the molecular details of binding interactions for these proteins. We propose to study these interactions as they occur in solution by using recombinant proteins expressed in E. coli, fluorescence and nuclear magnetic resonance spectroscopy, photoaffinity labeling, computer-assisted molecular modeling and mutagenesis experiments. We also propose to apply techniques developed to study the intracellular retinol binding proteins towards the analysis of intracellular retinoic acid binding proteins, including cellular retinoic acid binding protein (CRABP), and the nuclear retinoic acid binding proteins (including members of the RAR and RXR family).

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040172-06
Application #
2141208
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1989-09-15
Project End
1996-01-31
Budget Start
1994-02-01
Budget End
1995-01-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130