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Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.
- Source :
- Nature Structural & Molecular Biology; Jul2013, Vol. 20 Issue 7, p804-813, 10p, 3 Diagrams, 1 Chart, 5 Graphs
- Publication Year :
- 2013
-
Abstract
- HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1-V2, showing an epitope comprising both high mannose-type and complex-type N-linked glycans. We combined structure, NMR and mutagenesis analyses to characterize glycan recognition by PG9 and PG16. Three PG16-specific residues, arginine, serine and histidine (RSH), were critical for binding sialic acid on complex-type glycans, and introduction of these residues into PG9 produced a chimeric antibody with enhanced HIV-1 neutralization. Although HIV-1-glycan diversity facilitates evasion, antibody somatic diversity can overcome this and can provide clues to guide the design of modified antibodies with enhanced neutralization. [ABSTRACT FROM AUTHOR]
- Subjects :
- GLYCANS
IMMUNOGLOBULINS
GLYCOPEPTIDES
EPITOPES
SERINE
Subjects
Details
- Language :
- English
- ISSN :
- 15459993
- Volume :
- 20
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Nature Structural & Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 88899505
- Full Text :
- https://doi.org/10.1038/nsmb.2600