Prediction of the most favorable configuration in the ACBP–membrane interaction based on electrostatic calculations

VALLEJO, DF; F. ZAMARREÑO; GUERIN, DM; J. RAUL GRIGERA; COSTABEL, MD

Biochimica et Biophysica Acta - Biomembranes

Elsevier

Año: 2009 vol. 1788 p. 696 - 700

0005-2736

Acyl-CoA binding proteins (ACBPs) are highly conserved 10 kDa cytosolic proteins that bind medium- andlong-chain acyl-CoA esters. They act as intracellular carriers of acyl-CoA and play a role in acyl-CoAmetabolism, gene regulation, acyl-CoA-mediated cell signaling, transport-mediated lipid synthesis,membrane trafficking and also, ACBPs were indicated as a possible inhibitor of diazepam binding to theGABA-A receptor. To estimate the importance of the non-specific electrostatic energy in the ACBP–membraneinteraction, we computationally modeled the interaction of HgACBP with both anionic and neutralmembranes. To compute the Free Electrostatic Energy of Binding (dE), we used the Finite Difference PoissonBoltzmann Equation (FDPB) method as implemented in APBS. In the most energetically favorable orientation,ACBP brings charged residues Lys18 and Lys50 and hydrophobic residues Met46 and Leu47 into membranesurface proximity. This conformation suggests that these four ACBP amino acids are most likely to play aleading role in the ACBP–membrane interaction and ligand intake. Thus, we propose that long rangeelectrostatic forces are the first step in the interaction mechanism between ACBP and membranes.© 2008 Elsevier B.V. All rights reserved.