Journal article
Monoclonal Antibody m18 Paratope Leading to Dual Receptor Antagonism of HIV-1 gp120
Biochemistry (Easton), v 50(14), pp 2769-2779
12 Apr 2011
PMID: 21417283
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We sought to identify sequences in the monoclonal antibody m18 complementarity determining regions (CDRs) that are responsible for its interaction with HIV-1 gp120 and inhibition of the envelope receptor binding sites. In the accompanying paper, we reported that m18 inhibits CD4 binding through a non-activating mechanism that, at the same time, induces conformational effects leading to inhibition of the coreceptor site. Here, we sought to define the structural elements in m18 responsible for these actions. Direct binding and competition analyses using surface plasmon resonance showed that YU-2 gp120 binding is stabilized by a broad paratope of residues in the m18 CDRs. Additionally, several m18 residues were identified for which mutants retained high affinity for gp120, but had suppressed CD4 and 17b inhibition activities. A subset of these mutants did, however, neutralize HXBc2 viral infection. The results obtained in this work demonstrate that the combined m18 paratope contains subsets of residues that are differentially important for the binding and inhibition functions of the m18 neutralizing antibody. The data also add to prior observations that high affinity antibodies that do not inhibit monomeric gp120 receptor site interactions may still exhibit significant antiviral activity.
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Details
- Title
- Monoclonal Antibody m18 Paratope Leading to Dual Receptor Antagonism of HIV-1 gp120
- Creators
- Syna Kuriakose Gift - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Karyn McFadden - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Isaac J Zentner - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Srivats Rajagopal - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Mei-Yun Zhang - AIDS Institute; Department of Microbiology, The University of Hong Kong, Hong KongDimiter S Dimitrov - Center for Cancer Research Nanobiology Program, CCR, NCI-Frederick, NIH, Frederick, Maryland 21702Irwin M Chaiken - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102
- Publication Details
- Biochemistry (Easton), v 50(14), pp 2769-2779
- Publisher
- American Chemical Society; Washington, DC
- Grant note
- P01 GM056550-16 || GM / National Institute of General Medical Sciences : NIGMS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000289029200008
- Scopus ID
- 2-s2.0-79953727282
- Other Identifier
- 991014877962704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology