Unknown

Dataset Information

0

Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.


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.

SUBMITTER: Pancera M 

PROVIDER: S-EPMC4046252 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 an  ...[more]

Similar Datasets

| S-EPMC3406929 | biostudies-literature
| S-EPMC3421697 | biostudies-literature
| S-EPMC4125441 | biostudies-literature
| S-EPMC7418894 | biostudies-literature
| S-EPMC4157072 | biostudies-literature
| S-EPMC5101508 | biostudies-literature
| S-EPMC5806907 | biostudies-other
2019-12-10 | GSE141679 | GEO
| S-EPMC8296142 | biostudies-literature
| S-EPMC4777393 | biostudies-literature