4ZMJ

Crystal Structure of Ligand-Free BG505 SOSIP.664 HIV-1 Env Trimer

Summary for 4ZMJ

• Entry DOI: 10.2210/pdb4zmj/pdb
• Descriptor: Envelope glycoprotein gp160, 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, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: hiv-1, env trimer, unliganded, bg505 sosip, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 2
• Total formula weight: 76450.64

Authors

Kwon, Y.D.,Kwong, P.D. (deposition date: 2015-05-04, release date: 2015-06-24, Last modification date: 2024-10-16)

Primary citation

Do Kwon, Y.,Pancera, M.,Acharya, P.,Georgiev, I.S.,Crooks, E.T.,Gorman, J.,Joyce, M.G.,Guttman, M.,Ma, X.,Narpala, S.,Soto, C.,Terry, D.S.,Yang, Y.,Zhou, T.,Ahlsen, G.,Bailer, R.T.,Chambers, M.,Chuang, G.Y.,Doria-Rose, N.A.,Druz, A.,Hallen, M.A.,Harned, A.,Kirys, T.,Louder, M.K.,O'Dell, S.,Ofek, G.,Osawa, K.,Prabhakaran, M.,Sastry, M.,Stewart-Jones, G.B.,Stuckey, J.,Thomas, P.V.,Tittley, T.,Williams, C.,Zhang, B.,Zhao, H.,Zhou, Z.,Donald, B.R.,Lee, L.K.,Zolla-Pazner, S.,Baxa, U.,Schon, A.,Freire, E.,Shapiro, L.,Lee, K.K.,Arthos, J.,Munro, J.B.,Blanchard, S.C.,Mothes, W.,Binley, J.M.,McDermott, A.B.,Mascola, J.R.,Kwong, P.D.
Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env.
Nat.Struct.Mol.Biol., 22:522-531, 2015

PubMed Abstract: As the sole viral antigen on the HIV-1-virion surface, trimeric Env is a focus of vaccine efforts. Here we present the structure of the ligand-free HIV-1-Env trimer, fix its conformation and determine its receptor interactions. Epitope analyses revealed trimeric ligand-free Env to be structurally compatible with broadly neutralizing antibodies but not poorly neutralizing ones. We coupled these compatibility considerations with binding antigenicity to engineer conformationally fixed Envs, including a 201C 433C (DS) variant specifically recognized by broadly neutralizing antibodies. DS-Env retained nanomolar affinity for the CD4 receptor, with which it formed an asymmetric intermediate: a closed trimer bound by a single CD4 without the typical antigenic hallmarks of CD4 induction. Antigenicity-guided structural design can thus be used both to delineate mechanism and to fix conformation, with DS-Env trimers in virus-like-particle and soluble formats providing a new generation of vaccine antigens.

PubMed: 26098315
DOI: 10.1038/nsmb.3051

Experimental method

X-RAY DIFFRACTION (3.31 Å)