5V7J

Crystal Structure at 3.7 A Resolution of Glycosylated HIV-1 Clade A BG505 SOSIP.664 Prefusion Env Trimer with Four Glycans (N197, N276, N362, and N462) removed in Complex with Neutralizing Antibodies 3H+109L and 35O22.

Summary for 5V7J

• Entry DOI: 10.2210/pdb5v7j/pdb
• Descriptor: Envelope glycoprotein gp160, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-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, ... (16 entities in total)
• Functional Keywords: hiv-1, envelope, antibody, virus, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 183203.78

Authors

Stewart-Jones, G.B.E.,Zhou, T.,Kwong, P.D. (deposition date: 2017-03-20, release date: 2017-06-21, Last modification date: 2024-11-20)

Primary citation

Zhou, T.,Doria-Rose, N.A.,Cheng, C.,Stewart-Jones, G.B.E.,Chuang, G.Y.,Chambers, M.,Druz, A.,Geng, H.,McKee, K.,Kwon, Y.D.,O'Dell, S.,Sastry, M.,Schmidt, S.D.,Xu, K.,Chen, L.,Chen, R.E.,Louder, M.K.,Pancera, M.,Wanninger, T.G.,Zhang, B.,Zheng, A.,Farney, S.K.,Foulds, K.E.,Georgiev, I.S.,Joyce, M.G.,Lemmin, T.,Narpala, S.,Rawi, R.,Soto, C.,Todd, J.P.,Shen, C.H.,Tsybovsky, Y.,Yang, Y.,Zhao, P.,Haynes, B.F.,Stamatatos, L.,Tiemeyer, M.,Wells, L.,Scorpio, D.G.,Shapiro, L.,McDermott, A.B.,Mascola, J.R.,Kwong, P.D.
Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation.
Cell Rep, 19:719-732, 2017

PubMed Abstract: While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.

PubMed: 28445724
DOI: 10.1016/j.celrep.2017.04.013

Experimental method

X-RAY DIFFRACTION (2.907 Å)