6DE7

Crystal Structure at 4.3 A Resolution of Glycosylated HIV-1 Clade A BG505 SOSIP.664 Prefusion Env Trimer with Interdomain Stabilization 113C-429GCG in Complex with Broadly Neutralizing Antibodies PGT122 and 35O22

Summary for 6DE7

• Entry DOI: 10.2210/pdb6de7/pdb
• Descriptor: Envelope glycoprotein gp160, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[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, ... (15 entities in total)
• Functional Keywords: hiv-1, sosip, disulfide, trimer, immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 180581.75

Authors

Gorman, J.,Kwong, P.D. (deposition date: 2018-05-11, release date: 2018-06-06, Last modification date: 2024-10-09)

Primary citation

Zhang, P.,Gorman, J.,Geng, H.,Liu, Q.,Lin, Y.,Tsybovsky, Y.,Go, E.P.,Dey, B.,Andine, T.,Kwon, A.,Patel, M.,Gururani, D.,Uddin, F.,Guzzo, C.,Cimbro, R.,Miao, H.,McKee, K.,Chuang, G.Y.,Martin, L.,Sironi, F.,Malnati, M.S.,Desaire, H.,Berger, E.A.,Mascola, J.R.,Dolan, M.A.,Kwong, P.D.,Lusso, P.
Interdomain Stabilization Impairs CD4 Binding and Improves Immunogenicity of the HIV-1 Envelope Trimer.
Cell Host Microbe, 23:832-844.e6, 2018

PubMed Abstract: The HIV-1 envelope (Env) spike is a trimer of gp120/gp41 heterodimers that mediates viral entry. Binding to CD4 on the host cell membrane is the first essential step for infection but disrupts the native antigenic state of Env, posing a key obstacle to vaccine development. We locked the HIV-1 Env trimer in a pre-fusion configuration, resulting in impaired CD4 binding and enhanced binding to broadly neutralizing antibodies. This design was achieved via structure-guided introduction of neo-disulfide bonds bridging the gp120 inner and outer domains and was successfully applied to soluble trimers and native gp160 from different HIV-1 clades. Crystallization illustrated the structural basis for CD4-binding impairment. Immunization of rabbits with locked trimers from two different clades elicited neutralizing antibodies against tier-2 viruses with a repaired glycan shield regardless of treatment with a functional CD4 mimic. Thus, interdomain stabilization provides a widely applicable template for the design of Env-based HIV-1 vaccines.

PubMed: 29902444
DOI: 10.1016/j.chom.2018.05.002

Experimental method

X-RAY DIFFRACTION (4.123 Å)