Abstract
We examined the ligand protein interactions of two highly homologous cellular retinol binding proteins, CRBP and CRBP-II, and two highly homologous cellular retinoic acid binding proteins, CRABP-I and CRABP-II. While the crystal structures of all four have been determined, nuclear magnetic resonance studies provide a means for observing dynamic aspects of ligand protein interactions of these proteins in solution. The cellular functions of these proteins are less well understood. We have modeled retinoid flux between cytoplasmic retinoid proteins and model membranes and with nuclear receptors. Based on our in vitro studies, we propose that certain retinoids may indirectly influence retinoid signaling by displacing endogenous retinoids from the cytoplasmic proteins to the nuclear receptors.
Similar content being viewed by others
References
Li E, Norris AW: Structure/function of cytoplasmic vitamin A-binding proteins. Ann Rev Nutr 16: 205–234, 1996
Ong DE, Newcomer ME, Chytil F: Cellular retinoid-binding proteins. In: M.B. Sporn, A.B. Roberts, D.S. Goodman (eds). The Retinoids: Biology, Chemistry, and Medicine, Raven Press, New York, 1994, pp 283–317
Mangelsdorf DJ, Evans RM: The RXR heterodimers and orphan receptors (review). Cell 83: 841–850, 1995
Cowan SW, Newcomer ME, Jones TA: Crystallographic studies on a family of cellular lipophilic transport proteins. J Mol Biol 230: 1225–1246, 1993
Winter NS, Bratt JM, Banaszak LJ: The crystal structure of holo-and apo-cellular retinol binding protein II. J Mol Biol 230: 1247–1259, 1993
Kleywegt GJ, Bergfors T, Senn H, Le Motte P, Gsell B, Studo K, Jones TA: Crystal structure of cellular retinoic acid binding proteins I and II in complex with all-trans-retinoic acid and a synthetic retinoid. Structure 2: 1241–1258, 1994
Thompson JR, Bratt JM, Banaszak LJ: Crystal structures of cellular retinoic acid binding protein I show increased access to the binding cavity due to formation of an intermolecular β-sheet. J Mol Biol 252: 433–436, 1995
Norris AW, Cheng L, Giguère V, Rosenberger M, Li, E: Measurement of sub-nanomolar retinoic acid binding affinities for cellular retinoic acid binding proteins by fluorometric titration. Biochem Biophys Acta 1209: 10–18, 1994
Tian K-P, Norris AW, Lin C-LS, Li E: The isolation and characterization of purified heterocomplexes of recombinant retinoic acid receptor and retinoid X receptor ligand binding domains. Biochemistry 36: 5669–5676, 1997
Boylan JF, Gudas LJ: Overexpression of the cellular retinoic acid binding protein I (CRABP-I) results in a reduction in differentiation-specific gene expression in F9 teratocarcinoma stem cells. J Cell Biol 112: 965–979, 1991
Venepally P, Reddy LG, Sani BP: Analysis of the effects of CRABP-I expression on the RA-induced transcription mediated by retinoid receptors. Biochemistry 35: 9974–9982, 1996
De Bruijn DRH, Oerlemans F, Hendriks W, Baats E, Ploemacher R, Wieringa B, Guerts van Kessel: Normal development, growth and reproduction in cellular retinoic acid binding protein-I (CRABP-I) null mutant mice. Differentiation 58: 141–148, 1994
Gorry P, Luffin T, Dierich A, Rochette-Egly C, Décimo D, Dollè P, Mark M, Durand B, Chambon P: The cellular retinoic acid binding protein I is dispensable. Proc Natl Acad Sci USA 91: 9032–9036, 1994
Fawcett D, Pasceri P, Fraser R, Colbert M, Rossant J, Gigurère V: Postaxial polydactyly in forelimbs of CRABP-II mutant mice. Development 121: 671–679, 1995
Lampron C, Rochette-Egly C, Gorry P, Dollé P, Mark M, Lufkin T, LeMeur M, Chambon P: Mice deficient in cellular retinoic acid binding protein II (CRABP-II) or in both CRABP-I and CRABP-II are essentially normal. Development 121: 539–548, 1995
Norris AW, Rong D, d'Avignon DA, Rosenberger M, Tasaki K, Li E: Nuclear magnetic resonance studies demonstrate differences in the interaction of retinoic acid with two highly homologous cellular retinoic acid binding proteins. Biochemistry 34: 15564–15573, 1995
Honig B, Hudson B, Sykes BD, Karplus M: Ring orientation in β-ionone and retinals. Proc Natl Acad Sci USA 68: 1289–1293, 1971
Li E, Qian S, Yang NC, d'Avignon A, Levin MS, Gordon JI: Fluorine nuclear magnetic resonance analysis of the ligand binding properties of two homologous rat cellular retinol binding proteins expressed in Escherichia coli. J Biol Chem 265: 11549–11554, 1991
Rong D, Lin C-LS, d'Avignon DA, Lovey AJ, Rosenberger M, Li E: 19F-NMR studies of retinol transfer between cellular retinol binding proteins and phospholipid vesicles. FEBS Lett 402: 116–120
Levin MS: Cellular retinol binding proteins are determinants of retinol uptake and metabolism in stably transfected Caco-2 cells. J Biol Chem 268: 8267–8276, 1993
Lissoos TW, Davis AE, Levin MS: Vitamin A trafficking in Caco-2 cells stably transfected with cellular retinol binding proteins. Am J Physiol 268: G224–G231, 1995
Troen G, Eskild W, Fromm SH, Reppe S, Nilsson A, Norum KR, Blomhoff R: Retinyl ester storage is normal in transgenic mice with enhanced expression of cellular retinol binding protein I. J Nutr 123: 2709–2719, 1996
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Li, E. Structure and function of cytoplasmic retinoid binding proteins. Mol Cell Biochem 192, 105–108 (1999). https://doi.org/10.1023/A:1006882622898
Issue Date:
DOI: https://doi.org/10.1023/A:1006882622898