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

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

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Summary: 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 Personal Hygiene 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 Boys Jackets CD4bs recognition.