| Description: |
The lipocalins are a diverse, interesting, yet poorly understood family of proteins composed, in the main, of extracellular ligand-binding proteinsdisplaying high specificity for small hydrophobic molecules [, ]. Functions of these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration and the enzymatic synthesis of prostaglandins.The crystal structures of several lipocalins have been solved and show an 8-stranded anti-parallel β-barrel fold well conserved within thefamily. Sequence similarity within the family is at a much lower level and would seem to be restricted to conserved disulphides and 3 motifs, whichform a juxtaposed cluster that may act as a common cell surface receptor site []. By contrast, at the more variable end of the fold are found an internal ligand binding site and a putative surface for the formation of macromolecular complexes []. The anti-parallel β-barrel fold is also exploited by the fatty acid-binding proteins (which function similarly by binding small hydrophobic molecules), by avidin and the closely related metalloproteinase inhibitors, and by triabin. Similarity at the sequence level, however, is less obvious, being confined to a single short N-terminal motif. The lipocalin family can be subdivided into kernal and outlier sets. The kernal lipocalins form the largest self consistent group, comprising the subfamily of prostaglandin D synthases. The outlier lipocalins form several smaller distinct subgroups: the OBPs, the von Ebner's gland proteins, alpha-1-acid glycoproteins, tick histamine binding proteins and the nitrophorins.Glutathione-independent prostaglandin D (PGD2) synthase () is the main factor involved in synthesis of PGD2 in the brain, accounting for over 90% of activity in the rat; it is responsible for catalysing the conversion of PGH2 into PGD2 in the presence of various thiol compounds. PGD2 is a major prostaglandin in mammalian brains, functioning in the central nervous system as both a neuromodulator and a trophic factor. In peripheral tissues, it is involved in vasodilation and bronchoconstriction and it also mediates allergy and inflammatory responses []. The enzymatic activity of PGD synthase makes it unique among the lipocalins. It is localised in the choroid plexus, meninges and oligodendrocytes, but is also a major component of cerebrospinal fluid. Immunocytochemistry indicates that the protein is associated with the rough endoplasmic reticulum and the outer nuclear membranes of rat oligodendrocytes, and seems to be a peripheral membrane protein easily dissociated by detergents. A near homologue of PGD2 synthase has been identified in cane-toad (Bufo marinus) choroid plexus, where it is the most abundant protein secreted into the cerebrospinal fluid []. It is also found in other areas of the brain, albeit at much lower levels, and is expressed throughout amphibian metamorphosis. The choroid plexus helps form the barrier between blood and cerebrospinal fluid, and it has been suggested that this lipocalin may help transport lipophilic molecules across the blood/brain barrier. |
