Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

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

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Pancera, M.
  • Shahzad-ul-Hussan, S.
  • Doria-Rose, N. A.
  • McLellan, J. S.
  • Bailer, R. T.
  • Dai, K.
  • Loesgen, S.
  • Louder, M. K.
  • Staupe, R. P.
  • Yang, Y.
  • Zhang, B.
  • Parks, R.
  • Eudailey, J.
  • Lloyd, K. E.
  • Blinn, J.
  • Alam, S. M.
  • Haynes, B. F.
  • Amin, M. N.
  • Wang, L. X.
  • Burton, Dennis
  • Koff, W. C.
  • Nabel, G. J.
  • Mascola, J. R.
  • Bewley, C. A.
  • Kwong, P. D.

publication date

  • July 2013

journal

  • Nature Structural & Molecular Biology  Journal

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.

subject areas

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Antibodies, Neutralizing
  • Antibody Specificity
  • Antigen-Antibody Reactions
  • Binding Sites, Antibody
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Crystallography, X-Ray
  • Epitopes
  • Glycosylation
  • HEK293 Cells
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Humans
  • Immunoglobulin Fab Fragments
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments
  • Polysaccharides
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Structure-Activity Relationship
  • Swainsonine
scroll to property group menus

Identity

PubMed Central ID

  • PMC4046252

International Standard Serial Number (ISSN)

  • 1545-9993

Digital Object Identifier (DOI)

  • 10.1038/nsmb.2600

PubMed ID

  • 23708607
scroll to property group menus

Additional Document Info

start page

  • 804

end page

  • 813

volume

  • 20

issue

  • 7

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support