How fatty acids bind to proteins: the inside story from protein structures

The interactions of fatty acids with proteins have been probed with a great variety of techniques and strategies. Many approaches have substituted covalently labeled fatty acids or structurally related molecules. Information from such studies ultimately requires validation by studies with natural fatty acids. However, even the best conventional approaches with natural fatty acids generally have revealed only limited aspects of fatty acid-protein interactions. In contrast, recent crystallographic and NMR studies of several proteins with bound fatty acids provide complete three-dimensional structures with molecular details of these interactions. This presentation reviews three examples of proteins that are indirectly or directly involved in cell signaling: a protein in the plasma compartment (human serum albumin); a protein family in the cytosolic compartment of mammalian cells (fatty-acid-binding proteins), and a nuclear protein (peroxisome proliferator-activated receptor): it also discusses the structures of these proteins and their binding pocket(s), compares their specific modes of interactions with fatty acids, and discusses established and potential roles of fatty acid-protein interactions in cell signaling.