Characterization of a Lipophilin in Rabbit Tears

Abstract

A novel protein in human tears called lipophilin has homology to the uteroglobin superfamily.^1–3 Putative functions of the members of the family include the binding of hydrophobic molecules, anti-inflammatory properties, anti-chemotactic properties, suppression of extracelluar matrix invasion by normal and cancer cells, and phospholipase A₂ inhibition.^4,5 Other proteins in the uteroglobin family include rat prostatem⁶ (a steroid binding protein), uteroglobin^7,8 (a progesterone binding protein), Clara cell protein⁸ (a phosphatidylcholine and phosphatidylinositol binding protein), and mammaglobin⁹. The proteins share some structural features. In general, monomers are linked by disulfide bonds to form homo- (uteroglobin, Clara cell protein) or hetero-dimers (human lipophilin and prostatein). The crystal structure of uteroglobin reveals that the dimer is composed of two independent polypeptide chains of 70 residues linked by two disulfide bridges. Each monomer is folded into four alpha-helices. An oblong hydrophobic pocket composes the putative progesterone-binding site.¹⁰ The rat and human Clara cell protein also exists as 2 identical monomers joined together in an antiparallel manner to enclose a large internal hydrophobic cavity.^8,11 The structural motif common to all members of the family is a hydrophobic tunnel created by the alpha helical monomers and bridged by multiple disulfide bonds. The disulfide bonds may be important in ligand binding and release. For uteroglobin, a reduction in the bonds induces a local unfolding of the N- and C-termini. The resulting separation of helices creates a channel to the binding site.¹²