Retinol-binding protein structure

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.)...

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. 

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. 

Godovac-Zimmermann, J., Conti, A., Liberatori, J., and Braunitzer, G. 1985. Homology between the primary structures of beta-lactoglobulins and human retinol-binding protein Evidence for a similar biological function Biol Chem Hoppe Seyler 366(4) 431-434. 

Figure 4.13 Anatomy of selected proteins. (A) The /3 subunit of hemoglobin carrying a heme molecule (B) triose isomerase and (C) /3-lactoglobulin carrying a molecule of vitamin A. Spirals represent helix segments, and the broad arrows are pleated sheet polypeptide segments showing the direction from the N to the C terminus. (A and B reproduced with permission from Richardson JS. The anatomy and taxonomy of protein structure. Adv Prot Chem 34 168-339, 1981. C reproduced with permission from Papiz MZ, Sawyer L, Eliopoulos EE, North ACT, Findlay JBC, Sivaprasadarao R, Jones TA, Newcomer ME, Kraulis PJ. The structure of beta-lactoglobulin and its similarity to plasma retinol-binding protein. Nature 324 383-385, 1986.)...

Fig. 4-8 Stylized representations of protein structures in which a helices are represented as coiled ribbons and p strands are represented by arrows pointing in the N — C direction, p proteins contain predominantly /3-sheet structure (e.g., retinol binding protein and the antigen binding fragment of antibodies) while a proteins contain predominantly a helices (e.g., myoglobin), alp proteins contain a mixture of a helix and p sheet (e.g., triosephosphate isomerase).

Fig. 4-10 Topology diagram for (a) retinol binding protein (RBP) and (b) triosephosphate isomerase (TPI). The arrows represent p strands (numbered from N to C) and the dark boxes represent a helices. Note from Fig. 4-8 that both of these proteins form a barrel structure comprised of eight p strands with the first strand hydrogen bonded to last strand in order to "close the barrel. However, whereas the p strands are antiparallel in RBP, they are arranged in parallel in TPI and are surrounded by an outer layer of a helices which connect each p strand to the next in the barrel.

The lipocalin superfamily of over 20 structurally related secreted proteins have heen extensively used as biochemical markers of disease. Some of the more well-known hpocahns include retinol-binding protein. Protein HC (a -microglobulin, a -m), and human neutrophil lipocahn/ neutrophil gelatinase-associated lipocalin (HNL/NGAL) [110]. 

X. Members of eLBP Family with Known Crystal Structure A. Serum Retinol-Binding Protein... 

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. 

Pervaiz S, Brew K. Homology and structure-function correlations between tti-acid glycoprotein and serum retinol-binding protein and its relatives. FASEB J 1987 1 209-14. 

Calderone, V., C. Folli, A. Marchesani, R. Bemi and G. Zanotti. Identification and structural analysis of a zebrafish apo- and holo-cellular retinol-binding protein. J. Mol. Biol. 321 527—535, 2002. 

Transthyretin amyloidosis (also called familial amyloid polyneuropathy) is an autosomal dominant syndrome characterized by peripheral neuropathy. This disease results from one of five mutations identified thus far in the gene for transthyretin. Transthyretin is also called prealbumin (although it has no structural relationship to albumin) because it migrates ahead of albumin in standard electrophoresis at pH 8.6. Transthyretin is synthesized in the liver and is a normal plasma protein with a concentration of 20-40 mg/dL. It transports thyroxine and retinol binding protein (Chapter 38). The concentration of transthyretin is significantly decreased in malnutrition and plasma levels are diagnostic of disorders of malnutrition (Chapter 17). 

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. 

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