Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
Copyright policy )Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
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.
- National Institute of Allergy and Infectious Diseases United States
- Columbia University United States
- North Carolina State University United States
- National Institutes of Health United States
- University of North Carolina at Chapel Hill United States
Models, Molecular, QH301-705.5, Protein Conformation, glycan276, CD4 binding site, Article, antibody-antigen binding, Epitopes, Structure-Activity Relationship, Antibody Specificity, Polysaccharides, Humans, Biology (General), AIDS Vaccines, Cryoelectron Microscopy, env Gene Products, Human Immunodeficiency Virus, glycan conformation, Single Molecule Imaging, antibody approach angle, HEK293 Cells, CD4 Antigens, HIV-1, cryo-EM, Binding Sites, Antibody, Broadly Neutralizing Antibodies, Protein Binding
Models, Molecular, QH301-705.5, Protein Conformation, glycan276, CD4 binding site, Article, antibody-antigen binding, Epitopes, Structure-Activity Relationship, Antibody Specificity, Polysaccharides, Humans, Biology (General), AIDS Vaccines, Cryoelectron Microscopy, env Gene Products, Human Immunodeficiency Virus, glycan conformation, Single Molecule Imaging, antibody approach angle, HEK293 Cells, CD4 Antigens, HIV-1, cryo-EM, Binding Sites, Antibody, Broadly Neutralizing Antibodies, Protein Binding
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