A Fast Electrostatic Study to Determinate Fatty Acid Binding Protein – Membrane Interaction Mechanism.

FERNANDO ZAMARREÑO; MARÍA J. AMUNDARAIN; NESTOR E. SANCHEZ FORNILLO; MARCELO D. COSTABEL

Salta

Congreso; XXXIX Annual Meeting of The Argentinean Biophysical Society 2010, Workshop CeBEM & 3rd Latin American Protein Society Meeting.; 2010

SAB, LAPS y otras.

The study of reversible protein membrane interactions provides insights into cellular physiology, and has a deep impact in biotechnology and medicine. Examples of this kind of proteins are fatty acid binding proteins (FABP) which have been implicated in processes that facilitate lipid solubilization and movement in the cellular milieu. FABP belongs to a family of intracellular lipid binding proteins with the general function of lipid trafficking. The precise physiological functions of these proteins are as yet unclear, but it is hypothesized that they are important in intracellular transport and targeting of FA to specific membranes and metabolic pathways. In vitro studies have shown that different FABPs transfer FA to membranes by two different transfer mechanisms. Liver FABPs transfers ligand to and from membranes by aqueous phase diffusion. In marked contrast, a larger number of FABPs, including adipocyte, intestinal, brain, and heart/muscle types, transfer their FA by directly interacting with a membrane (“collisional” mechanism). To get insight into the mechanism, we modeled computationally the process for different FABPs, considering, as is generally accepted, the electrostatic interaction as the first step in the mechanism. Finally, we studied the minimums in the electrostatics interaction energy difference to discriminate among possible membrane-bound models of the set of FABPs, suggesting, in each case, a most probable orientation of the protein in the vicinity of the membrane and, in this way, differentially select between possible mechanisms.