Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site

Nat Struct Mol Biol. 2016 Oct;23(10):906-915. doi: 10.1038/nsmb.3291. Epub 2016 Sep 12.


HIV-1 vaccine design is informed by structural studies elucidating mechanisms by which broadly neutralizing antibodies (bNAbs) recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env). Variability in high-mannose and complex-type Env glycoforms leads to heterogeneity that usually precludes visualization of the native glycan shield. We present 3.5-Å- and 3.9-Å-resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation, revealing a glycan shield of high-mannose and complex-type N-glycans, which we used to define complete epitopes of two bNAbs. Env trimer was complexed with 10-1074 (against the V3-loop) and IOMA, a new CD4-binding site (CD4bs) antibody. Although IOMA derives from VH1-2*02, the germline gene of CD4bs-targeting VRC01-class bNAbs, its light chain lacks the short CDRL3 that defines VRC01-class bNAbs. Thus IOMA resembles 8ANC131-class/VH1-46-derived CD4bs bNAbs, which have normal-length CDRL3s. The existence of bNAbs that combine features of VRC01-class and 8ANC131-class antibodies has implications for immunization strategies targeting VRC01-like bNAbs.

MeSH terms

  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology
  • CD4 Antigens / chemistry
  • CD4 Antigens / immunology*
  • Crystallography, X-Ray
  • Epitopes / analysis
  • Epitopes / immunology
  • Glycosylation
  • HIV Antibodies / chemistry
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Envelope Protein gp120 / immunology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / chemistry*
  • HIV-1 / immunology
  • Humans
  • Mannose / analysis*
  • Mannose / immunology
  • Models, Molecular
  • Polysaccharides / analysis*
  • Polysaccharides / immunology
  • Protein Conformation
  • Protein Multimerization


  • Antibodies, Neutralizing
  • CD4 Antigens
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Polysaccharides
  • Mannose