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Title: Mapping the binding interface between an HIV-1 inhibiting intrabody and the viral protein rev
Authors: Vercruysse, Thomas ×
Boons, Eline
Venken, Tom
Vanstreels, Els
Voet, Arnout
Steyaert, Jan
De Maeyer, Marc
Daelemans, Dirk #
Issue Date: Apr-2013
Publisher: Public Library of Sciene
Series Title: PLoS One vol:8 issue:4 pages:e60259
Article number: 10.1371/journal.pone.0060259
Abstract: HIV-1 Rev is the key protein in the nucleocytoplasmic export and expression of the late viral mRNAs. An important aspect for its function is its ability to multimerize on these mRNAs. We have recently identified a llama single-domain antibody (Nb190) as the first inhibitor targeting the Rev multimerization function in cells. This nanobody is a potent intracellular antibody that efficiently inhibits HIV-1 viral production. In order to gain insight into the Nb190-Rev interaction interface, we performed mutational and docking studies to map the interface between the nanobody paratope and the Rev epitope. Alanine mutants of the hyper-variable domains of Nb190 and the Rev multimerization domains were evaluated in different assays measuring Nb190-Rev interaction or viral production. Seven residues within Nb190 and five Rev residues are demonstrated to be crucial for epitope recognition. These experimental data were used to perform docking experiments and map the Nb190-Rev structural interface. This Nb190-Rev interaction model can guide further studies of the Nb190 effect on HIV-1 Rev function and could serve as starting point for the rational development of smaller entities binding to the Nb190 epitope, aimed at interfering with protein-protein interactions of the Rev N-terminal domain.
URI: 
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Biochemistry, Molecular and Structural Biology Section
× corresponding author
# (joint) last author

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