MULTIPLE MOLECULAR RECOGNITION PROPERTIES OF THE LIPOCALIN PROTEIN FAMILY

The lipocalins, a diverse family of small extracellular ligand binding proteins, display a remarkable range of different molecular recognition properties. While their binding of small hydrophobic molecules, and to a lesser extent their binding to cell surface receptors, is well known, it is shown here that formation of macromolecular complexes is also a common feature of this family. Analysis of known crystallographic structures reveals that the lipocalins possess a conserved common structure: an antiparallel beta-barrel with a repeated +1 topology. Comparisons show that within this overall similarity the structure of individual proteins is specifically adapted to bind their particular ligands, forming a binding site from an internal cavity (within the barrel) and/or an external loop scaffold, which gives rise to different binding modes that reflects the need to accommodate ligands of different shape, size, and chemical structure. The architecture of the lipocalin fold suggests that both the ends and sides of this barrel are topologically distinct, differences also apparent in analyses of structural and sequence variation within the family. These differences can be linked to experimental evidence suggesting a possible functional dichotomy between the two ends of the lipocalin fold. The structurally invariant end of the molecule may be implicated in general binding to common cell surface receptors, while the more variable end is adapted to the specialised tasks of binding small ligands and forming macromolecular complexes via an exposed binding surface.