7LG6

BG505 SOSIP.v5.2 in complex with VRC40.01 and RM19R Fabs

Summary for 7LG6

• Entry DOI: 10.2210/pdb7lg6/pdb
• EMDB information: 23312
• Descriptor: Envelope glycoprotein gp120, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• Functional Keywords: antibody, hiv, sosip, env, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 18
• Total formula weight: 526219.81

Authors

Cottrell, C.A.,Torres, J.L.,Wu, N.R.,Ward, A.B. (deposition date: 2021-01-19, release date: 2021-09-15, 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 (3.28 Å)