Binding of retinol in both retinoid-binding sites of interphotoreceptor retinoid-binding protein (IRBP) is stabilized mainly by hydrophobic interactions.
Interphotoreceptor retinoid-binding protein (IRBP) is an ocular protein which is believed to participate in the visual cycle by mediating transport of retinoids between pigment epithelium and photoreceptor cells. The molecular mechanism underlying the ability of IRBP to target particular retinoids to the specific cells that are their sites of action and metabolism is not completely clear, and little information is available regarding the structure of the protein's multiple ligand-binding sites. IRBP possesses two retinoid-binding sites, and it was reported that binding of the visual chromophore, 11-cis-retinal, in one of these sites, but not in the other, is tightly regulated by another IRBP ligand, docosahexaenoic acid (Chen, Y., Houghton, L. A., Brenna, J. T., and Noy, N. (1996) J. Biol. Chem. 271, 20507). The two sites are thus functionally distinct. Here, the thermodynamic parameters governing the interactions of retinol with the IRBP retinoid-binding sites were measured. The data demonstrate that the interactions of retinol with both sites are stabilized mainly by hydrophobic interactions, and that the hydroxyl head group of retinol is not involved in formation of protein-ligand complexes. Nevertheless, the data indicate that the two sites are structurally distinct, and that binding of retinol in them occurs by remarkably different modes of interactions.
Tschanz
C L
CL
Division of Nutritional Sciences, Savage Hall, Cornell University, Ithaca, New York 14853, USA. nn14@cornell.edu
Noy
N
N
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D005123:Eye; D005136:Eye Proteins / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D011485:Protein Binding; D012177:Retinol-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D013696:Temperature; D013816:Thermodynamics; D014801:Vitamin A / Q000737:chemistry* / Q000378:metabolism; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D014801:Vitamin A; D000099214:Retinol-Binding Proteins, Interstitial