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Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies

Journal Article · · Cell Reports
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  1. The Scripps Research Inst., La Jolla, CA (United States)
  2. Duke Univ., Durham, NC (United States)
  3. National Institutes of Health (NIH), Bethesda, MD (United States)
  4. Univ. of North Carolina, Chapel Hill, NC (United States)
  5. National Institutes of Health (NIH), Bethesda, MD (United States); Columbia Univ., New York, NY (United States)
  6. 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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