Interactions of the Fatty Acid-Binding Protein ReP1-NCXSQ with Lipid Membranes. Influence of the Membrane Electric Field on Binding and Orientation.

VANESA V GALASSI; MARCOS A. VILLARREAL; VELIA POSADA; GUILLERMO G. MONTICH

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014 vol. 1838 p. 910 - 920

0005-2736

The regulatory protein of the squid nerve sodium calciumexchanger  (ReP1-NCXSQ) is a 15 kDa soluble, intracellular protein that regulates  the activity of the Na+/Ca2+ exchanger in the squid axon. It is a member  of the cellular retinoic acid-binding proteins family and the fatty acid-binding proteins superfamily. It is composed of ten beta strands defining an inner cavity and a domain of two short alpha helix segments.  In this work, we studied the binding and orientation of ReP1-NCXSQ in  anionic and zwitterionic lipid membranes using molecular dynamics (MD)  simulations. Binding to lipid membranes was also measured by  filtration binding assay. ReP1-NCXSQ acquired an orientation in the  anionic membranes with the positive end of the macrodipole pointing to  the lipid membrane. Potential of mean force calculations, in agreement  with experimental measurements, showed that the binding to the anionic  interfaces in low ionic strength was stronger than the binding to anionic  interfaces in high ionic strength or to zwitterionic membranes. The  results of MD showed that the electrostatic binding can bemediated not  only by defined patches or domains of basic residues but also by a global  asymmetric distribution of charges. A combination of dipole?electric field  interaction and local interactions determined the orientation of  ReP1-NCXSQ in the interface.