Structure-Function Studies of Lipid Binding Proteins

University Of Minnesota-Twin Cities, Minneapolis MN

Investigators

Abstract

The prevalence of water-insoluble compounds in biological systems has driven the evolutionary development of families of hydrophobic ligand carrier proteins. Just as there are carrier proteins that function to solubilize and deliver hydrophobic molecules in the circulatory system (e.g., lipoprotein particles, albumin, etc.), there exists a homologous family of proteins that are found intracellularly. These proteins, which have been termed the fatty acid binding proteins (FABPs), are responsible for the solubilization and delivery of hydrophobic ligands within a cell. The FABPs bind most avidly to fatty acids and retinoids. The signature feature of all FABPs is a Beta-barrel fold forming an internal, water-filled cavity that serves as the ligand-binding domain. A 1:1 non-covalent complex is typically formed between the protein and the ligand and once inside, the ligand is sequestered from the external milieu. The adipocyte FABP (FABP4) has been studied in detail as a model for structure-function relationships of the fatty acid binding proteins. The investigators hypothesize that FABP4 functions to donate insoluble long chain fatty acids to acyl CoA synthetase producing a soluble lipid (acyl CoA). To test this hypothesis, they will: (I) evaluate the effect of FABP4 on the catalytic activity and ligand binding properties of very long chain acyl CoA synthetase and (ii) examine the physical interaction of FABP4 with the acyl CoA synthetase using microcalorimetry and map the interaction site(s).