Ligand retinol-binding protein

Van Aalten, D.M.F., Findlay, J.B.C., Amadei, A., Berendsen,H.J.C. Essential dynamics of the cellular retinol-binding protein. Evidence for ligand-induced conformational changes. Protein Engin. 8 (1995) 1129-1136. 

Thus, it is possible to calculate the off-rates of protein-ligand interactions observed for individual amino acid residues of the protein of a verified reaction mechanism. A nice example that shows various cases was recently published for the Apo-Cellular Retinol Binding Protein (97). 

Mittag T, et al. Retinol modulates site-specific mobility of 118. apo-cellular retinol-binding protein to promote ligand binding. 

Serum retinol-binding protein (RBP) is a retinoid-binding protein found in the circulatory system. The protein is synthesized in the hepato-cytes, where it accumulates until the presence of its ligand in the circulation triggers the secretion of the complex (Ronne et cd., 1983 Good-... 

Wang, B., Merz, K.M. Validation of the binding site structure of the cellular retinol-binding protein (CRBP) by ligand NMR chemical shift perturbations. J. Am. Chem. Soc. 2005,127, 5310-1. 

Ronne H, Ocklind C, Wiman K, Rask L, Obrink B, Peterson PA. Ligand dependent regulation of intracellular protein transport effect of vitamin A on the secretion of retinol-binding protein. J Cell Biol 1983 96 907-10. 

Most of these proteins are also responsible for the inter and intracellular transport of the hydrophobic ligands, otherwise insoluble in a polar environment. Retinol binding protein [5], bilin binding protein [7], insecticyanin [2] and P-lactoglobulin [5,... 

The first lipocalin whose 3-D structure was solved and refined at high resolution was the human plasma retinol-binding protein (RBP) [22, 23]. RBP acts as a natural transporter of vitamin A (retinol) in the blood of vertebrates. Upon complexation in a hydrophobic cavity with complementary shape, the poorly soluble terpenoid alcohol becomes packaged by the protein and protected from oxidation or double-bond isomerization. RBP is synthesized in the liver and directly loaded with fhe hgand in fhe hepatocyte, where retinol is stored. Furthermore, the holo-RBP forms a structurally defined ternary complex with transthyretin [24], also known as prealbumin. After delivery of the retinol ligand to a target tissue, fhe complex decomposes and fhe monomeric apo-RBP becomes filtered out by fhe kidney and degraded. 

Fig. 13.11. Binding of retinol to the active site of retinol binding protein (IRBP, stereo-diagram). The ligand is completely encapsulated in the protein with the y -ionone ring in the center and the unsaturated isoprene chromophore stretching to the solvent surface along the main axis of the fi barrel packing motif in this protein...

The peculiar spectral properties of CRBP-bound retinol and RME are indicative of specific ligand-protein interactions (see Fig. 2) Instead, other holo-retinoid-binding proteins exhibit less characteristic spectra. For example the absorption spectrum of the complex of retinol with plasma retinol-binding protein (RBP) is characterized by a single, well-shaped peak centered at approx 328 nm On the other hand, the absorption spectra of some CRBP-bound retinoids, like CRBP-bound a l-trans retinal (12,13), do not resemble those of CRBP-bound retinol and RME. 

Although it has been shown to be capable of binding retinaldehyde and retinoic acid (Liou et al., 1982c), as well as a-tocopherol (Liou et al., 1983), the major endogenous ligand of interstitial retinol-binding protein appears to be... 

Interstitial retinol-binding protein may also carry other lipid-soluble ligands vitamin E is one possibility (Seetion II,F,2). This compound is present in bovine... 

Hydrophobic compounds are transported in plasma bound to transport proteins (e.g. the plasma retinol binding protein section 11.2.2.2) or dissolved in the lipid core of plasma lipoproteins (section 5.6.2), and net intracellular accumulation to a higher concentration than in plasma depends on an intracellular binding protein that has a greater affinity for the ligand than does the plasma transport protein. 

Penzes P, Napoli JL (1999) Holo-cellular retinol-binding protein distinction of ligand-binding affinity from efficiency as substrate in retinal biosynthesis. Biochemistry 38 2088-2093... 

Mata, N. L. Phan, K. Han, Y. Assay of retinol-binding protein-transthyretin interaction and techniques to identify competing ligands. Methods Mol. Biol. 2010,652,209-227. 

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