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

Los Cocos, Córdoba, Argentina

Congreso; XXXVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2009

Siciedad Argentina Biofísica

<!-- @page { margin: 0.79in } P { margin-bottom: 0.08in } --> The fatty acid-binding protein ReP1 is a soluble protein that regulates the activity of Na+/Ca2+ transporter. It is composed of the common beta-barrel motif with ten beta-strands and two alpha-helix that form the portal region. Its isoelectric point of 5.85 leads to a net charge of -1 at neutral pH. It has been found that ReP1 interacts with anionic lipids such as phosphatidilinositols and phosphatidic acid [1]. Because of this capacity, ReP1 is a good model to test the hypothesis that the binding and the orientation of soluble proteins within lipid membranes is driven by the interaction of its macrodipole with the electric field of the interface [2]. This is also an alternative and attractive model to explain the binding of proteins with net charge of the same sign as the interface. We calculated the macrodipole of ReP1. It has a magnitude of 450 Debyes and a direction pointing towards the portal region of the barrel. We performed molecular dynamic simulations to study the interaction of ReP1 with anionic lipid membranes. We observed that the protein migrated from two initial configurations in the aqueous phase, to the interface of the anionic lipid membrane. The protein acquired an orientation in which the macrodipole is aligned in the configuration of lowest energy within the electric field of the interface. In this protein, this orientation correspond to the portal (alfa helix) region located in contact with the membrane. In a previous work with L-BABP [2], a protein with identical tertiary structure, the portal region was distal to the membrane, but in coincidence with the present results, its macrodipole is aligned in the conformation of lowest energy. It was not found a significant conformational change in ReP1 during the 30 ns of simulation. [1] G. Berberián, M. Bollo, G. Montich, G. Roberts, JA. DeGiorgis, R. DiPolo, L. Beaugé, Biochimica et Biophysica Acta, 2009, 1788, 1255–1262. [2] MA. Villarreal, M. Perduca, HL. Monaco, GG. Montich, Biochimica et Biophysica Acta, 2008, 1778, 1390–1397. <!-- @page { margin: 0.79in } P { margin-bottom: 0.08in } -->