Interaction of a Peripheral Acidic Protein with Anionic Lipid Membranes: Insights from Molecular Simulations

VANESA V. GALASSI; MARCOS A. VILLARREAL; LUIS BEAUGE; MARIANA BOLLO; GRACIELA BERBERIAN; GUILLERMO G. MONTICH

Salta

Congreso; 3rd Latin American Protein Society Meeting - XXXIX Annual Meeting of the Argentinean Biophysical Sociey ? Workshop CeBEM ? Structural Biology in Latin America; 2010

The fatty acid-binding protein ReP1 is a soluble protein that shows the common beta-barrel motif with two alfa-helix in the portal region. Its isoelectric point of 5.85 leads to net charge of -1 at neutral pH. Previous evidence of its interaction with anionic lipids [1], makes it an attractive model to test the hypothesis that the binding and orientation of soluble proteins to lipid membranes is driven by the interaction of its macrodipole with the interphasial electric field [2]. The interaction of ReP1 with lipid membranes of anionic and zwitterionic phospholipids was studied by multiple-run molecular dynamics, Potential of Mean Force calculations and filtration assays. ReP1 has a macrodipole of 310 Debyes pointing towards the portal region. We found that it interacted selectively with anionic interphases, aligning its macrodipole in the configuration of lowest energy within the membrane electric field. This led the portal region to be in contact with the membrane. The strength and range of the interaction and orientation was attenuated by the presence of salt. A loss of secondary structure was observed in the region farther from the membrane, which was suppressed by the presence of salt. A similar behaviour has been described for L-BABP [2], a protein with identical tertiary structure.These electrostatic-like features of the interaction suggest that the interphasial electric field could be a driving force for the orientation and conformational change of peripheral proteins, and may be involved on the ligand delivery mechanism in this family of proteins.[1] BerberiánG., Bollo M., Montich G., Roberts G., DeGiorgis JA., DiPolo R.,Beaugé L., Biochimicaet Biophysica Acta,1788, 1255?1262(2009).[2] VillarrealMA., Perduca M., Monaco HL., MontichGG., Biochimicaet Biophysica Acta,1778, 1390?1397 (2008).