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. 

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

Tlie retinol-binding protein binds retinol inside an up-and-down fi barrel... 

The first example is the plasma-borne retinol-binding protein, RBP, which is a single polypeptide chain of 182 amino acid residues. This protein is responsible for transporting the lipid alcohol vitamin A (retinol) from its storage site in the liver to the various vitamin-A-dependent tissues. It is a disposable package in the sense that each RBP molecule transports only a single retinol molecule and is then degraded. 

Figure S.3 Schematic diagram of the structure of human plasma retinol-binding protein (RBP), which is an up-and-down P barrel. The eight antiparallel P strands twist and curl such that the structure can also be regarded as two p sheets (green and blue) packed against each other. Some of the twisted p strands (red) participate in both P sheets. A retinol molecule, vitamin A (yellow), is bound inside the barrel, between the two P sheets, such that its only hydrophilic part (an OH tail) is at the surface of the molecule. The topological diagram of this stmcture is the same as that in Figure 5.2. (Courtesy of Alwyn Jones, Uppsala, Sweden.)...

Figure S.S Amino acid sequence of p strands 2 3 4 in human plasma retinol-binding protein. The sequences are listed in such a way that residues which point into the barrel are aligned. These hydrophobic residues are arrowed and colored green. The remaining residues are exposed to the solvent.

The retinol-binding protein belongs to a superfarnily of protein structures... 

Godovac-Zimmerman, J. The structural motif of p-lactoglobulin and retinol-binding protein a basic framework for binding and transport of small hydrophobic molecules Trends Biochem. Sci. 

Newcomer, M.E., et al. The three-dimensional structure of retinol-binding protein. EMBO J. 

In rhino viruses there are depressions, or "canyons," which are 25 A deep and 12 to 30 A wide and which encircle the protrusions (Figure 16.15b). One wall of the canyons is lined by residues from the base of VPl. The structure of VPl is such that the barrel is open at the base and permits access to the hydrophobic interior of the barrel, as in the up-and-down barrel structure of the retinol-binding protein described in Chapter 5. 

Hemopexin (binds heme) Retinol-binding protein (binds retinol) Sex hormone-binding globulin (binds testosterone, estradiol) Thyroid-binding globulin (binds T4, T3) Transferrin (transport iron)... 

Transthyretin (formerly prealbumin binds T4 and forms a complex with retinol-binding protein)... 

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

Honkanen, R.D., Kontinnen, Y.T. and Mussalo-Rauhamaa, H. (1989). Vitamins A and E, retinol binding protein and zinc in rheumatoid arthritis. Clin. Exp. Rheum. 7, 465-469. 

Monitoring of Cd exposure can take place by the determination of Cd in whole blood (reflects recent exposure) or urine (reflects body burden) by GF-AAS. Early effects can be monitored by the determination of a tubular protein (e.g. 132-microglobulin, retinol binding protein, a2-microglobulin) or the activity of an enzyme (e.g. N-acetyl 3-D-glucosaminidase) in urine. 

Lee K.-H., Wells R.G. and Reed R. (1987). Isolation of an olfactory complementary DNA similarity to retinol-binding protein suggests a role in olfaction. Science 253, 1053-1066. 

The other major class of extracellular LBPs of mammals is the lipocalins (Flower, 1996). These are approximately 20 kDa, P-sheet-rich proteins, performing functions such as the transport of retinol in plasma or milk, the capture of odorants in olfaction, invertebrate coloration, dispersal of pheromones, and solubilizing the lipids in tears (Flower, 1996). The retinol-binding protein (RBP) of human plasma is found in association with a larger protein, transthyretin, the complex being larger than the kidney threshold and thus not excreted, although the RBP itself may dissociate from the complex to interact with cell surface receptors in the delivery of retinol (Papiz et al., 1986 Sundaram et al., 1998). 

Kennedy, M.W., Garside, L.H., Goodrick, L.E., McDermott, L., Brass, A., Price, N.C., Kelly, S.M., Cooper, A. and Bradley, J.E. (1997) The Ov20 protein of the parasitic nematode Onchocerca volvulus. A structurally novel class of small helix-rich retinol-binding protein. Journal of Biological Chemistry 272, 29442-29448. 

Nirmalan, N., Cordeiro, N.J.V., Klager, S.L., Bradley, J.E. and Allen, J.E. (1999) Comparative analysis of glycosylated and non-glycosylated filarial homologues of the 20-kilodalton retinol binding protein from Onchocerca volvulus (Ov20). Infection and Immunity 67, 6239-6334. 

Sundaram, M., Sivaprasadarao, A., DeSousa, M.M. and Findlay, J.B.C. (1998) The transfer of retinol from serum retinol-binding protein to cellular retinolbinding protein is mediated by a membrane receptor. Journal of Biological Chemistry 273, 3336—3342. 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

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