title: A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield.
abstract: The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of antigen-binding fragments (Fabs) PGT 127 and 128 with Man(9) at 1.65 and 1.29 angstrom resolution, respectively, and glycan binding data delineate a specific high mannose-binding site. Fab PGT 128 complexed with a fully glycosylated gp120 outer domain at 3.25 angstroms reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short β-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificity. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 immunoglobulin Gs may be mediated by cross-linking Env trimers on the viral surface.
authors: Department of Molecular Biology, Skaggs Institute for Chemical Biology and International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, nhe Scripps Research Institute, La Jolla, CA 92037, USA.
authors: Robert
authors: R
authors: Pejchal
authors: Katie J
authors: KJ
authors: Doores
authors: Laura M
authors: LM
authors: Walker
authors: Reza
authors: R
authors: Khayat
authors: Po-Ssu
authors: PS
authors: Huang
authors: Sheng-Kai
authors: SK
authors: Wang
authors: Robyn L
authors: RL
authors: Stanfield
authors: Jean-Philippe
authors: JP
authors: Julien
authors: Alejandra
authors: A
authors: Ramos
authors: Max
authors: M
authors: Crispin
authors: Rafael
authors: R
authors: Depetris
authors: Umesh
authors: U
authors: Katpally
authors: Andre
authors: A
authors: Marozsan
authors: Albert
authors: A
authors: Cupo
authors: Sebastien
authors: S
authors: Maloveste
authors: Yan
authors: Y
authors: Liu
authors: Ryan
authors: R
authors: McBride
authors: Yukishige
authors: Y
authors: Ito
authors: Rogier W
authors: RW
authors: Sanders
authors: Cassandra
authors: C
authors: Ogohara
authors: James C
authors: JC
authors: Paulson
authors: Ten
authors: T
authors: Feizi
authors: Christopher N
authors: CN
authors: Scanlan
authors: Chi-Huey
authors: CH
authors: Wong
authors: John P
authors: JP
authors: Moore
authors: William C
authors: WC
authors: Olson
authors: Andrew B
authors: AB
authors: Ward
authors: Pascal
authors: P
authors: Poignard
authors: William R
authors: WR
authors: Schief
authors: Dennis R
authors: DR
authors: Burton
authors: Ian A
authors: IA
authors: Wilson
mesh_terms: D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D002236:Carbohydrate Conformation; D002460:Cell Line; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism; D000939:Epitopes; D006031:Glycosylation; D015483:HIV Antibodies / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008358:Mannose / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008362:Mannosides / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D057134:Antibodies, Neutralizing; D004187:Disaccharides; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; D008362:Mannosides; D009844:Oligosaccharides; D011134:Polysaccharides; C475460:mannosyl alpha(1-6)-mannoside; D008358:Mannose