Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site
Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site
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.
- University Hospital Cologne Germany
- University of Bonn Germany
- Rockefeller University United States
- University of Cologne Germany
- Howard Hughes Medical Institute United States
Models, Molecular, 570, Glycosylation, Protein Conformation, 610, HIV Infections, HIV Antibodies, HIV Envelope Protein gp120, Crystallography, X-Ray, Antibodies, Neutralizing, Epitopes, Polysaccharides, CD4 Antigens, HIV-1, Humans, Protein Multimerization, Mannose
Models, Molecular, 570, Glycosylation, Protein Conformation, 610, HIV Infections, HIV Antibodies, HIV Envelope Protein gp120, Crystallography, X-Ray, Antibodies, Neutralizing, Epitopes, Polysaccharides, CD4 Antigens, HIV-1, Humans, Protein Multimerization, Mannose
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