Lipid-Binding Proteins: A Family of Fatty Acid and Retinoid Transport Proteins

This chapter focuses on the structural analyses and comparisons between members of a multigene family of hydrophobic ligand-binding proteins. It discusses the structural motif, general characteristics of the binding cavity, ligand entry, and the portal hypothesis and provides a detailed comparison of intra- and extracellular lipid binding proteins with known crystal structures. The members of this family are referred as lipid-binding proteins (LBPs). This collection of proteins can be subdivided into two groups: the intracellular lipid-binding protein family (iLBP) and the extracellular lipid binding protein family (eLBP). The comparison primarily deals with the iLBP branch because this family is becoming structurally well characterized. However, the structural comparisons are extended to some members of the eLBP family because the basic structural motif used to bind hydrophobic ligands applies to both. The products of hydrolysis of the intestinal lipids, including fatty acids, cholesterol, monoglycerides, and lysophospholipids, have very low solubilities and are absorbed by biliary micelles in the gut. These micelles diffuse through the glycocalyx, which stabilizes an unstirred water layer at the surface of the enterocyte. The chapter concludes with a discussion of the results of site-directed mutagenesis studies, the thermodynamics of lipid binding, and considerations of protein stability and folding.