CIQUIBIC   05472
CENTRO DE INVESTIGACIONES EN QUIMICA BIOLOGICA DE CORDOBA
Unidad Ejecutora - UE
artículos
Título:
Binding and interactions of L-BABP to lipid membranes studied by molecular dynamic simulations
Autor/es:
VILLARREAL MA, PERDUCA M, MONACO HL, MONTICH GG.
Revista:
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Referencias:
Año: 2008 p. 1390 - 1397
ISSN:
0005-2736
Resumen:
Chicken liver bile acid-binding protein (L-BABP) is a member of the
fatty acid-binding proteins super family. The common fold is a
beta-barrel of ten strands capped with a short helix-loop-helix motif
called portal region, which is involved in the uptake and release of
non-polar ligands. Using multiple-run molecular dynamics simulations we
studied the interactions of L-BABP with lipid membranes of anionic and
zwitterionic phospholipids. The simulations were in agreement with our
experimental observations regarding the electrostatic nature of the
binding and the conformational changes of the protein in the membrane.
We observed that L-BABP migrated from the initial position in the
aqueous bulk phase to the interface of anionic lipid membranes and
established contacts with the head groups of phospholipids through the
side of the barrel that is opposite to the portal region. The
conformational changes in the protein occurred simultaneously with the
binding to the membrane. Remarkably, these conformational changes were
observed in the portal region which is opposite to the zone where the
protein binds directly to the lipids. The protein was oriented with its
macrodipole aligned in the configuration of lowest energy within the
electric field of the anionic membrane, which indicates the importance
of the electrostatic interactions to determine the preferred
orientation of the protein. We also identified this electric field as
the driving force for the conformational change. For all the members of
the fatty acid-binding protein family, the interactions with lipid
membranes is a relevant process closely related to the uptake, release
and transfer of the ligand. The observations presented here suggest
that the ligand transfer might not necessarily occur through the domain
that directly interacts with the lipid membrane. The interactions with
the membrane electric field that determine orientation and
conformational changes described here can also be relevant for other
peripheral proteins.