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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Cottrell, CA; Manne, K; Kong, R; Wang, S; Zhou, T; Chuang, G-Y; Edwards, RJ; Henderson, R; Janowska, K; Kopp, M; Lin, BC; Louder, MK; Olia, AS; Rawi, R; Shen, C-H; Taft, JD; Torres, JL; Wu, NR; Zhang, B; Doria-Rose, NA; Cohen, MS; Haynes, BF; Shapiro, L; Ward, AB; Acharya, P; Mascola, JR; Kwong, PD

Published Date

  • November 2021

Published In

Volume / Issue

  • 37 / 5

Start / End Page

  • 109922 -

PubMed ID

  • 34731616

Pubmed Central ID

  • PMC9058982

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

International Standard Serial Number (ISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2021.109922

Language

  • eng