7LY9

Cryo-EM structure of 2909 Fab in complex with 3BNC117 Fab and CAP256.wk34.c80 SOSIP.RnS2 N160K HIV-1 Env trimer

Summary for 7LY9

• Entry DOI: 10.2210/pdb7ly9/pdb
• EMDB information: 23589
• Descriptor: 2909 Light Chain, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: cap256, v1v2, v2-apex, sosip, vaccine, tys, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 14
• Total formula weight: 422724.33

Authors

Gorman, J.,Kwong, P.D. (deposition date: 2021-03-06, release date: 2021-08-18, Last modification date: 2025-05-14)

Primary citation

Lee, M.,Changela, A.,Gorman, J.,Rawi, R.,Bylund, T.,Chao, C.W.,Lin, B.C.,Louder, M.K.,Olia, A.S.,Zhang, B.,Doria-Rose, N.A.,Zolla-Pazner, S.,Shapiro, L.,Chuang, G.Y.,Kwong, P.D.
Extended antibody-framework-to-antigen distance observed exclusively with broad HIV-1-neutralizing antibodies recognizing glycan-dense surfaces.
Nat Commun, 12:6470-6470, 2021

PubMed Abstract: Antibody-Framework-to-Antigen Distance (AFAD) - the distance between the body of an antibody and a protein antigen - is an important parameter governing antibody recognition. Here, we quantify AFAD for ~2,000 non-redundant antibody-protein-antigen complexes in the Protein Data Bank. AFADs showed a gaussian distribution with mean of 16.3 Å and standard deviation (σ) of 2.4 Å. Notably, antibody-antigen complexes with extended AFADs (>3σ) were exclusively human immunodeficiency virus-type 1 (HIV-1)-neutralizing antibodies. High correlation (R = 0.8110) was observed between AFADs and glycan coverage, as assessed by molecular dynamics simulations of the HIV-1-envelope trimer. Especially long AFADs were observed for antibodies targeting the glycosylated trimer apex, and we tested the impact of introducing an apex-glycan hole (N160K); the cryo-EM structure of the glycan hole-targeting HIV-1-neutralizing antibody 2909 in complex with an N160K-envelope trimer revealed a substantially shorter AFAD. Overall, extended AFADs exclusively recognized densely glycosylated surfaces, with the introduction of a glycan hole enabling closer recognition.

PubMed: 34753907
DOI: 10.1038/s41467-021-26579-z

Experimental method

ELECTRON MICROSCOPY (3.91 Å)