Dissecting the carbohydrate specificity of the anti-HIV-1 2G12 antibody by single-molecule force spectroscopy.
Langmuir
; 28(51): 17726-32, 2012 Dec 21.
Article
em En
| MEDLINE
| ID: mdl-23198686
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína gp120 do Envelope de HIV
/
HIV-1
/
Microscopia de Força Atômica
/
Manose
/
Anticorpos Monoclonais
/
Especificidade de Anticorpos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Langmuir
Assunto da revista:
QUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Espanha