Lipocalin structure and function.

The lipocalins are a family of proteins the common function of which is to bind small hydrophobic substances. Although the amino-acid sequence similarity among the members of the family is low, there are two regions where the sequences are conserved. These are GXW and TDY (where X is usually acidic) [ 11. X-ray crystallography of several members of the family revealed that they exhibit a high degree of three-dimensional structural similarity, with the common structure motifs occupying identical spatial positions. The basic core of the structure is a /?-barrel with eight antiparallel Bstrands that fold into an orthogonal calyx [2, 31. The B-barrel is lined internally by many hydrophobic residues that confer ligand specificity. The highest degree of variation is found in the size, amino-acid sequence and spatial positions of loops that connect the /?-strands. This suggests that these loops may represent regions that are involved in the functional properties of particular proteins. We demonstrate this by taking human serum retinol-binding protein (RBP) as an example. RHP transports retinol from the liver to tissues requiring vitamin A. In the plasma, most RBP is found as a complex with another protein that is called transthyretin (TTR; for a review, see [4]). We have previously demonstrated that the transfer of retinol from RBP to vitamin-A-requiring cells involves the specific interaction of RBP with a plasma-membrane-bound receptor [ 51. The transfer of retinol to the target cell leaves RBP in a form that has a much reduced affinity for the receptor [6], as well as for TTR, and hence the protein is lost by glomerular filtration. This process causes a shift in the equilibrium TTR-RBP + TTR + RBP, ensuring the availability of free RBP for the further delivery of retinol. The structural changes that render RHP inactive in this way have yet to be established. Thus RBP, in addition to binding retinol, exhibits two other molecular-recognition properties, that is, it interacts with TTR and with the membrane receptor. Residues of RBP that are involved in the interaction with retinol have been identified by ~ ~