7llk

Publication Abstract from PubMed

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.

Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies.,Cottrell CA, Manne K, Kong R, Wang S, Zhou T, Chuang GY, Edwards RJ, Henderson R, Janowska K, Kopp M, Lin BC, Louder MK, Olia AS, Rawi R, Shen CH, 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 Cell Rep. 2021 Nov 2;37(5):109922. doi: 10.1016/j.celrep.2021.109922. PMID:34731616^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.