Functional Analysis of Mammalian Soluble Lipid Binding Proteins

LISANDRO J. FALOMIR-LOCKART; GISELA R. FRANCHINI; EDUARDO DE GERÓNIMO; MARÍA XIMENA GUERBI; LUCIANA RODRIGUEZ SAWICKI; NATALIA BOTTASSO; BETINA CÓRSICO

Facultad de Farmacia y Bioquímica UBA

Jornada; HERRAMIENTAS MODERNAS PARA EL ESTUDIO DE ASPECTOS ESTRUCTURALES DE PROTEÍNAS; 2009

ACADEMIA NACIONAL DE FARMACIA Y BIOQUÍMICA

The evolution of different families of intracellular soluble lipid bindingproteins (SLBP) may be connected to the wide range of functions attributed tolipids as well as their low solubility in the cellular media. Among these SLBP, themammalian fatty acid binding proteins (FABP) are ubiquitously produced. Thelarge number of FABP types and the distinct expression pattern of each of themsuggest overlapping as well as distinct functions in specific tissues; based onspecific structural elements. Structure-function studies indicate that subtleconformational changes that occur upon ligand binding may promote distinctFABP-protein or FABP-membrane interactions that could define their specificity.We used a combination of in vitro and in cell studies to assess the differentialfunctionality of abundantly coexpressed FABP in the enterocyte. First, the use ofseveral structural variants highlighted the importance of the helical region andspecific residues have been identified in the Portal Domain, crucial for ligandtransport and membrane binding properties of FABP. On the other hand,modification of their expression in culture cells has an impact on several cellularprocesses, mainly lipid metabolism but also cell proliferation and differentiation.FABPs’ participation in regulating fatty acid metabolism, may ultimately impact onsystemic metabolism.