Dissecting the carbohydrate specificity of the anti-HIV-1 2G12 antibody by single-molecule force spectroscopy
Broadly neutralizing anti-HIV-1 monoclonal antibody 2G12 exclusively targets a conserved cluster of high-mannose oligosaccharides present on outer viral envelope glycoprotein gp120. This characteristic makes the otherwise immunogenically "silent" glycan shield of gp120 a tempting target fo...
| Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1992. - 28(2012), 51 vom: 21. Dez., Seite 17726-32 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2012
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| Zugriff auf das übergeordnete Werk: | Langmuir : the ACS journal of surfaces and colloids |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't 2G12 monoclonal antibody Antibodies, Monoclonal Broadly Neutralizing Antibodies HIV Antibodies HIV Envelope Protein gp120 gp120 protein, Human immunodeficiency virus 1 Mannose PHA4727WTP |
| Zusammenfassung: | Broadly neutralizing anti-HIV-1 monoclonal antibody 2G12 exclusively targets a conserved cluster of high-mannose oligosaccharides present on outer viral envelope glycoprotein gp120. This characteristic makes the otherwise immunogenically "silent" glycan shield of gp120 a tempting target for drug and vaccine design. However, immune responses against carbohydrate-based mimics of gp120 have failed to provide immunization against HIV-1 infection, highlighting the need to understand the molecular events that determine immunogenicity better. In this work, the unbinding kinetics of the gp120-2G12 (k(0) = 0.002 ± 0.09 s(-1), x(++) = 1.5 ± 1.2 nm), Man(4)-2G12 (k(0) = 0.35 ± 0.32 s(-1), x(++) = 0.6 ± 0.2 nm), and Man(5)-2G12 interactions were measured by single-molecule force spectroscopy. To our knowledge, this is the first single-molecule study aimed at dissecting the carbohydrate-antibody recognition of the gp120-2G12 interaction. We were able to confirm crystallographic models that show both the binding of the linear Man(4) arm to 2G12 and also the multivalent gp120 glycan binding to 2G12. These results demonstrate that single-molecule force spectroscopy can be successfully used to dissect the molecular mechanisms underlying immunity |
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| Beschreibung: | Date Completed 23.05.2013 Date Revised 10.12.2019 published: Print-Electronic ErratumIn: Langmuir. 2013 May 7;29(18):5630 Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/la303484e |