Binding of acid and basic FABPs to cationic lipid membranes: evidencing the role of the protein macrodipole in protein-membrane interaction

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

San Javier

Congreso; XLI Annual Meeting of the Argentinean Biophysical Society; 2012

Sociedad Argentina de Biofísica

P { margin-bottom: 0.21cm; }Wehave already shown that two FABPs interact with anionic membranes andnot with zwitterionic ones1-4.The interaction is independent on the net charge of the protein:ReP1-NXSQisnegatively charged (z=-1) while L-BABPbearspositive charge (z=+2) at pH=7. We proposed that this interaction isdriven, at least in part, by the interaction of the proteinmacro-dipole with the membrane electric field. These proteins show apreferred orientation in the charged interface, which results fromthe alignment of the macro-dipole in the membrane electric field 2,4.When bound to the interface, these proteins undergo a partialunfolding, losing some tertiary native contacts. The extent of thisconformational change correlates with the membrane electric fieldintensity2,3.Herewe experimentallyfound that both proteins can also bind cationic lipid membranes, afurther evidence of the dipolar character of the interaction. Thisstrongly supports that the interaction is driven by the orientationof the dipole of the protein within the electric field generated bycharges in the membrane, whether negative or positive.Theorientation of the proteins in cationic membranes was also studied bymolecular dynamics simulations. We found that the orientation wascompatible with the most favorable orientation of the macro-dipole inthe membrane electric field.1.V. Nolan, M. Perduca, HL. Monaco, B. Maggio,GG.Montich. BBA 1611(2003) 98-106.2.MA. Villarreal, M. Perduca, HL. Mónaco,GG. Montich. BBA 1778 (2008) 1390-1397.3.MB. Decca, VV. Galassi, M.Perduca, HL Mónaco, GG. Montich.J.Phys.Chem. B 114 (2010) 15141-15150.4. VV.Galassi, MA. Villarreal, V. Posada, GG. Montich. J.Phys.Chem. B. Manuscript under revision