7LL2

Cryo-EM structure of BG505 DS-SOSIP in complex with Glycan276-Dependent Broadly Neutralizing Antibody VRC33.01 Fab

Summary for 7LL2

• Entry DOI: 10.2210/pdb7ll2/pdb
• Related: 7LL1 7LLK
• EMDB information: 23412
• Descriptor: Envelope glycoprotein gp120, Envelope glycoprotein gp41, VRC33.01 Fab Heavy chain, ... (9 entities in total)
• Functional Keywords: bg505 ds-sosip, glycan276-dependent, glycan276, vrc33.01 fab, hiv-1, immune system, immune system-viral protein complex, immune system/viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 379889.72

Authors

Manne, K.,Acharya, P. (deposition date: 2021-02-03, release date: 2021-03-17, Last modification date: 2024-10-30)

Primary citation

Cottrell, C.A.,Manne, K.,Kong, R.,Wang, S.,Zhou, T.,Chuang, G.Y.,Edwards, R.J.,Henderson, R.,Janowska, K.,Kopp, M.,Lin, B.C.,Louder, M.K.,Olia, A.S.,Rawi, R.,Shen, C.H.,Taft, J.D.,Torres, J.L.,Wu, N.R.,Zhang, B.,Doria-Rose, N.A.,Cohen, M.S.,Haynes, B.F.,Shapiro, L.,Ward, A.B.,Acharya, P.,Mascola, J.R.,Kwong, P.D.
Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies.
Cell Rep, 37:109922-109922, 2021

PubMed Abstract: 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.

PubMed: 34731616
DOI: 10.1016/j.celrep.2021.109922

Experimental method

ELECTRON MICROSCOPY (3.73 Å)