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Gewählte Publikation:

Lorizate, M; Cruz, A; Huarte, N; Kunert, R; Pérez-Gil, J; Nieva, JL.
(2006): Recognition and blocking of HIV-1 gp41 pre-transmembrane sequence by monoclonal 4E10 antibody in a Raft-like membrane environment.
J Biol Chem. 2006; 281(51):39598-39606 FullText FullText_BOKU

Abstract:
The conserved (664)DKWASLWNWFNITNWLWYIK(68)3 (preTM) sequence preceding the transmembrane anchor of human immunodeficiency virus (HIV-1) gp41 glycoprotein subunit is accessible to the broadly neutralizing 4E10 antibody and, therefore, constitutes a potential target for vaccine design. Recently reported structural data are compatible with preTM insertion into the viral external membrane monolayer in the gp41 pre-fusion state (Zhu, P., Liu, J., Bess, J., Chertova, E., Lifson, J. D., Grise, H., Ofek, G. A., Taylor, K. A., and Roux, K. H. ( 2006) Nature 441, 847-852). Here we demonstrate that the broadly neutralizing 4E10 antibody is able to specifically block the membrane-restructuring activity of a peptide mimic inserted into membranes. Recognition and restructuring blocking occurred in the presence of cholesterol, whereas transmembrane versions as those promoted in 1-palmitoyl-2- oleoylphosphatidylcholine: sphingomyelin mixtures could not be effectively arrested. Spectrofluorimetric assays using rhodamine- labeled peptides revealed that recognition correlated better with pore-formation blocking than with membrane-fusion inhibition. The capacity of the antibody to recognize preTM peptides in a raft-like environment was further corroborated employing planar-supported lipid layers and fluorescence microscopy. These data support that membrane-bound epitope recognition by 4E10 results in clustering reorganization of preTM at the membrane interface. We propose that this process might interfere with the formation of fusion-competent complexes at the low spike densities existing in the HIV-1 membrane. This work comprises the first experimental report on a lipid-modulated antibody capacity to bind a membrane-bound epitope sequence and arrest its restructuring activity.
Autor*innen der BOKU Wien:
Kunert Renate
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Find related publications in this database (using NML MeSH Indexing)
Animals -
Antibodies, Monoclonal - chemistry
CHO Cells - chemistry
Cholesterol - chemistry
Cricetinae - chemistry
Epitopes - chemistry
HIV Envelope Protein gp41 - chemistry
Humans - chemistry
Kinetics - chemistry
Lipids - chemistry
Membrane Microdomains - chemistry
Models, Biological - chemistry
Peptides - chemistry
Protein Binding - chemistry
Spectrometry, Fluorescence - chemistry



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