Two highly conserved amino acids seem to lead FABP-Membrane interaction. A multimethodological in silico approach.

FERNANDO ZAMARREÑO; FERNANDO HERRERA; NESTOR E. SANCHEZ FORNILLO; ALEJANDRO GIORGETTI; BETINA CÓRSICO; MARCELO D. COSTABEL

San Miguel de Tucuman

Congreso; XLI Reunión Anual de la Sociedad Argentina de Biofísica; 2012

Sociedad Argentina de Biofísica

Fatty Acid Binding Protein (FABP) belongs to a family of intracellular lipid binding proteins with the general function oflipid trafficking. In vitroand in silicostudies have shown that different FABPs transfer fatty acids to membranes by two different mechanisms. Liver FABPs transfers ligands to and from membranes by aqueous phase diffusion in a so called ?difusional mechanism?. In marked contrast, a larger number of FABPs, including intestinal type, transfers their ligands by directly interacting with a membrane in a ?collisional mechanism?. To get insight into the mechanism, we modeled computationally the process for rat Intestinal and liver FABPs considering, as is generally accepted, the electrostatic interaction as the first step in the mechanism. In this way, we determined by punctual mutation of allcharged amino acids, two residues that appear to have a strong relevance to the electrostatic interaction. On the other hand, bioinformatics analysis point tothe same couples of residues as highly conserved in both FABPs. Finally, we studied membrane-protein interaction, for both wild type and mutated FABPs, by molecular dynamics. In summary, results were consistent in all methods, indicating that conserved residues have indeed a significant role in FABPs-membrane interaction.