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

Reference
Article Authors:Marie Pancera; Syed Shahzad-Ul-Hussan; Nicole A Doria-Rose; Jason S McLellan; Robert T Bailer; Kaifan Dai; Sandra Loesgen; Mark K Louder; Ryan P Staupe; Yongping Yang; Baoshan Zhang; Robert Parks; Joshua Eudailey; Krissey E Lloyd; Julie Blinn; S Munir Alam; Barton F Haynes; Mohammed N Amin; Lai-Xi Wang; Dennis R Burton; Wayne C Koff; Gary J Nabel; John R Mascola; Carole A Bewley; Peter D Kwong
Article Title:Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.
Reference Detail
Reference ID:1026080
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.
Date:2013
Reference Type:Literature
PubMed ID:23708607
Journal:Nat Struct Mol Biol
Journal Volume:20
Article Pages:804-13
Journal ISSN:1545-9985
Article Chemical List:Antibodies, Neutralizing;Epitopes;HIV Antibodies;HIV Envelope Protein gp120;HIV envelope protein gp120 (135-148);Immunoglobulin Fab Fragments;Peptide Fragments;Polysaccharides;gp120 protein, Human immunodeficiency virus 1;Swainsonine
Article MeSH List:Amino Acid Motifs; Amino Acid Sequence; Antibodies, Neutralizing(chemistry; immunology; metabolism); Antibody Specificity; Antigen-Antibody Reactions; Binding Sites, Antibody; Carbohydrate Conformation; Carbohydrate Sequence; Crystallography, X-Ray; Epitopes(chemistry; immunology; metabolism); Glycosylation(drug effects); HEK293 Cells; HIV Antibodies(chemistry; immunology; metabolism); HIV Envelope Protein gp120(chemistry; immunology; metabolism); Humans; Immunoglobulin Fab Fragments(immunology; metabolism); Models, Molecular; Molecular Sequence Data; Peptide Fragments(chemistry; immunology; metabolism); Polysaccharides(chemistry; immunology; metabolism); Protein Conformation; Protein Processing, Post-Translational(drug effects); Structure-Activity Relationship; Swainsonine(pharmacology)
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