Structural characterization of a highly-potent V3-glycan broadly neutralizing antibody bound to natively-glycosylated HIV-1 envelope

Nat Commun. 2018 Mar 28;9(1):1251. doi: 10.1038/s41467-018-03632-y.


Broadly neutralizing antibodies (bNAbs) isolated from HIV-1-infected individuals inform HIV-1 vaccine design efforts. Developing bNAbs with increased efficacy requires understanding how antibodies interact with the native oligomannose and complex-type N-glycan shield that hides most protein epitopes on HIV-1 envelope (Env). Here we present crystal structures, including a 3.8-Å X-ray free electron laser dataset, of natively glycosylated Env trimers complexed with BG18, the most potent V3/N332gp120 glycan-targeting bNAb reported to date. Our structures show conserved contacts mediated by common D gene-encoded residues with the N332gp120 glycan and the gp120 GDIR peptide motif, but a distinct Env-binding orientation relative to PGT121/10-1074 bNAbs. BG18's binding orientation provides additional contacts with N392gp120 and N386gp120 glycans near the V3-loop base and engages protein components of the V1-loop. The BG18-natively-glycosylated Env structures facilitate understanding of bNAb-glycan interactions critical for using V3/N332gp120 bNAbs therapeutically and targeting their epitope for immunogen design.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / immunology
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Crystallography, X-Ray
  • Epitopes / chemistry*
  • Glycosylation
  • HEK293 Cells
  • HIV Antibodies / chemistry*
  • HIV Antibodies / immunology
  • HIV Envelope Protein gp120 / immunology*
  • HIV Infections / immunology
  • HIV-1
  • Humans
  • Polysaccharides / chemistry*
  • Protein Binding
  • Protein Domains
  • Protein Multimerization
  • env Gene Products, Human Immunodeficiency Virus / immunology*


  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Polysaccharides
  • env Gene Products, Human Immunodeficiency Virus