Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
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- The Scripps Research Inst., La Jolla, CA (United States)
- Duke Univ., Durham, NC (United States)
- National Institutes of Health (NIH), Bethesda, MD (United States)
- Univ. of North Carolina, Chapel Hill, NC (United States)
- National Institutes of Health (NIH), Bethesda, MD (United States); Columbia Univ., New York, NY (United States)
- Duke Univ., Durham, NC (United States); National Institutes of Health (NIH), Bethesda, MD (United States)
Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH); National Science Foundation (NSF); Scripps CHAVD; USDOE Office of Science (SC), Basic Energy Sciences (BES); Vaccine Research Center
- Grant/Contract Number:
- W-31109-ENG-38
- OSTI ID:
- 1829863
- Journal Information:
- Cell Reports, Journal Name: Cell Reports Journal Issue: 5 Vol. 37; ISSN 2211-1247
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
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