6E5P

Backbone model based on cryo-EM map at 8.5 A of domain-swapped, glycan-reactive, neutralizing antibody 2G12 bound to HIV-1 Env BG505 DS-SOSIP, which was also bound to CD4-binding site antibody VRC03

Summary for 6E5P

• Entry DOI: 10.2210/pdb6e5p/pdb
• EMDB information: 8981
• Related PRD ID: PRD_900111
• Descriptor: 2G12 Light chain, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2G12 heavy chain, ... (10 entities in total)
• Functional Keywords: hiv-1 env, complex, neutralizing, viral protein, domain-swapped antibody
• Biological source: Homo sapiens; More
• Total number of polymer chains: 24
• Total formula weight: 658135.30

Authors

Acharya, P.,Kwong, P.D. (deposition date: 2018-07-21, release date: 2019-02-13, Last modification date: 2024-03-13)

Primary citation

Chuang, G.Y.,Zhou, J.,Acharya, P.,Rawi, R.,Shen, C.H.,Sheng, Z.,Zhang, B.,Zhou, T.,Bailer, R.T.,Dandey, V.P.,Doria-Rose, N.A.,Louder, M.K.,McKee, K.,Mascola, J.R.,Shapiro, L.,Kwong, P.D.
Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition.
Structure, 27:196-206.e6, 2019

PubMed Abstract: Over the past decade, structures have been determined for broadly neutralizing antibodies that recognize all major exposed surfaces of the prefusion-closed HIV-1-envelope (Env) trimer. To understand this recognition and its implications, we analyzed 206 antibody-HIV-1 Env structures from the Protein Data Bank with resolution suitable to define interaction chemistries and measured antibody neutralization on a 208-strain panel. Those with >25% breadth segregated into almost two dozen classes based on ontogeny and recognition and into six epitope categories based on recognized Env residues. For paratope, the number of protruding loops and level of somatic hypermutation were significantly higher for broad HIV-1 neutralizing antibodies than for a comparison set of non-HIV-1 antibodies (p < 0.0001). For epitope, the number of independent sequence segments was higher (p < 0.0001), as well as the glycan component surface area (p = 0.0005). The unusual characteristics of epitope and paratope delineated here are likely to reflect respectively virus-immune evasion and antibody-recognition solutions that allow effective neutralization of HIV-1.

PubMed: 30471922
DOI: 10.1016/j.str.2018.10.007

Experimental method

ELECTRON MICROSCOPY (8.8 Å)