Abstract
The cytosolic lipid-binding proteins (cLBPs) comprise a large family of small (14-15 kDa) intracellular proteins involved in the transport of small lipids, including fatty acids and retinoids within cells. Their presumed function is to solubilise, protect from chemical damage and deliver to the correct destination lipids for purposes ranging from energy metabolism (e.g. fatty acids) to signalling, gene activation and cellular differentiation (e.g. retinoids and eicosanoids). It is therefore probable that cLBPs interact directly with cellular components (membranes and/or proteins) to collect and deposit their ligands, and some external features of the different cLBPs may be involved in such interactions and determine which cellular component (integral membrane or cytosolic proteins, or membranes of different lipid compositions or domain structures) with which a given cLBP will interact. Here we have focussed on a previously unrecognised feature of cLBPs which descriminates between those for which there is empiral evidence for direct interaction with membranes, and those which do not. This is a group of bulky hydrophobic amino acid side chains (e.g. tryptophans, phenylalanines, leucines) which project directly into solvent adjacent to the portal of entry and exit of the lipid ligands. Such side chains are usually found internal to proteins, but are common at sites of protein:protein or protein:membrane interactions. These 'sticky fingers' could therefore be critical to the nature and specificity of the interactions cLBPs undergo in the web of cross-traffic in lipid movements within cells.