Epitopes described in "Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120."

Article Authors:Leopold Kong; Jeong Hyun Lee; Katie J Doores; Charles D Murin; Jean-Philippe Julien; Ryan McBride; Yan Liu; Andre Marozsan; Albert Cupo; Per-Johan Klasse; Simon Hoffenberg; Michael Caulfield; C Richter King; Yuanzi Hua; Khoa M Le; Reza Khayat; Marc C Deller; Thomas Clayton; Henry Tien; Ten Feizi; Rogier W Sanders; James C Paulson; John P Moore; Robyn L Stanfield; Dennis R Burton; Andrew B Ward; Ian A Wilson
Article Title:Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120.
Reference Detail
Reference ID:1026310
Abstract:A substantial proportion of the broadly neutralizing antibodies (bnAbs) identified in certain HIV-infected donors recognize glycan-dependent epitopes on HIV-1 gp120. Here we elucidate how the bnAb PGT 135 binds its Asn332 glycan-dependent epitope from its 3.1-Å crystal structure with gp120, CD4 and Fab 17b. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield and access the gp120 protein surface. EM reveals that PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. Combined structural studies of PGT 135, PGT 128 and 2G12 show that this Asn332-dependent antigenic region is highly accessible and much more extensive than initially appreciated, which allows for multiple binding modes and varied angles of approach; thereby it represents a supersite of vulnerability for antibody neutralization.
Affiliations:Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Reference Type:Literature
PubMed ID:23708606
Journal:Nat Struct Mol Biol
Journal Volume:20
Article Pages:796-803
Journal ISSN:1545-9993
Article Chemical List:Alkaloids;Antibodies, Neutralizing;Antigens, CD4;Biopolymers;Epitopes;HIV Antibodies;HIV Envelope Protein gp120;Immunoglobulin Fab Fragments;Polysaccharides;env Gene Products, Human Immunodeficiency Virus;gp120 protein, Human immunodeficiency virus 1;gp140 envelope protein, Human immunodeficiency virus 1;kifunensine;1-Deoxynojirimycin;miglustat
Article MeSH List:1-Deoxynojirimycin(analogs & derivatives; pharmacology); Alkaloids(pharmacology); Amino Acid Motifs; Amino Acid Sequence; Antibodies, Neutralizing(chemistry; immunology; metabolism); Antigen-Antibody Reactions; Antigens, CD4(immunology; metabolism); Binding Sites, Antibody; Biopolymers; Carbohydrate Sequence; Crystallography, X-Ray; Epitopes(chemistry; immunology); Glycosylation(drug effects); HEK293 Cells; HIV Antibodies(chemistry; immunology; metabolism); HIV Envelope Protein gp120(chemistry; immunology; metabolism; ultrastructure); Humans; Immunoglobulin Fab Fragments(immunology; metabolism); Microscopy, Electron; Models, Molecular; Molecular Docking Simulation; Molecular Sequence Data; Polysaccharides(physiology); Protein Conformation; Protein Processing, Post-Translational(drug effects); Structure-Activity Relationship; env Gene Products, Human Immunodeficiency Virus(immunology)
Curation Last Updated:2016-05-11 20:12:05