Molecular dynamics of the interaction of an acidic soluble protein with anionic lipid membranes

VANESA GALASSI, LUIS BEAUGÉ, MARIANA BOLLO, GRACIELA BERBERIÁN, MARCOS VILLARREAL, GUILLERMO MONTICH

Montevideo, Uruguay

Workshop; Computational Modelling and Simulation of Biological Systems; 2010

Institut Pasteur de Montevideo

The fatty acid-binding protein ReP1 is a soluble regulator of the Na+/Ca2+ transporter. Its tertiary structureis a beta-barrel motif with ten beta-strands and two alfa-helix that form the portal region. Its isoelectric point of5.85 leads to a net charge of -1 at neutral pH. It has been found to interact with anionic lipids [1]. Becauseof this, ReP1 is a good model to test the hypothesis that the binding of soluble proteins to lipidmembranes is driven by the interaction of its macrodipole with the interface electric field [2]. This is anattractive model to explain the binding of proteins with net charge of the same sign as the interface.We calculated the macrodipole of ReP1, which resulted in 450 Debyes pointing towards the portal of thebarrel. We performed simulations to study the interaction of ReP1 with anionic lipid membranes. Theprotein migrated from different initial configurations in the aqueous phase, to the interface of the anioniclipid membrane and acquired an orientation aligning the macrodipole in the configuration of lowestenergy within the interfacial electric field, leading to the portal region in contact to the membrane. In aprevious work with L-BABP [2], a protein with identical tertiary structure, the portal region is distal tothe membrane, but in coincidence with the present results, its macrodipole is aligned in the configurationof lowest energy.[1] G.Berberián, M.Bollo, G.Montich, G.Roberts, JA.DeGiorgis, R.DiPolo, L.Beaugé, BBA, 2009, 1788, 1255–1262.[2] MA.Villarreal, M.Perduca, HL.Monaco, GG.Montich, BBA, 2008, 1778, 1390–1397.