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Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling
Poster Abstracts
7-POS
Board 7
Cholesterol-dependent Membrane Fusion Induced by the HIV-1 GP41 MPER-TMD and
Blocking by Antibodies Functioning at Membrane Surfaces
Pablo Carravilla
1
, Edurne Rujas
1
, Beatriz Apellániz
1
, Aitziber Araujo
1
, Nerea Huarte
1
, Eneko
Largo
1
, Soraya Serrano
2
, Carmen Domene
3
, María A. Jiménez
2
, José L. Nieva
1
.
1
Biophysics Unit (CSIC, UPV/EHU) and Dept. of Biochemistry, University of the Basque
Country (UPV/EHU, P.O. Box 644, 48080 Bilbao, Spain,
2
Institute of Physical Chemistry
“Rocasolano” (CSIC), Serrano 119, E-28006 Madrid, Spain,
3
Chemistry Research Laboratory,
Mansfield Road, University of Oxford, Oxford OX1 3TA, United Kingdom.
Anti-HIV antibodies 4E10 and 10E8 neutralize practically all viral strains and isolates tested in
standard assays. These ‘pan-neutralizing’ antibodies bind to the gp41 membrane proximal
external region (MPER)-transmembrane domain (TMD) junction at the membrane surface of
virions poised for fusion and block the process. The resulting broad neutralization underscores
the conservation and functionality of the MPER-TMD region. In recent work, we have described
that peptides representing this region have potent membrane-destabilizing effects. Here, based on
the outcome of NMR structural studies, vesicle assays, atomic force microscopy characterization
and molecular dynamics simulations, we propose a mechanism for the involvement of the
MPER-TMD region in HIV-1 fusion, which is dependent on the high cholesterol content
accumulated in the viral envelope. In addition, we provide evidence that underpins the potential
use of its activity as a new target for inhibitor and immunogen development.