5W6D

Crystal structure of BG505-SOSIP.v4.1-GT1-N137A in complex with Fabs 35022 and 9H/109L

Summary for 5W6D

• Entry DOI: 10.2210/pdb5w6d/pdb
• Descriptor: BG505-SOSIP.v4.1-GT1-N137A gp120, 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, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (13 entities in total)
• Functional Keywords: hiv-1 broadly neutralizing antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 6
• Total formula weight: 176226.50

Authors

Garces, F.,Stanfield, R.L.,Wilson, I.A. (deposition date: 2017-06-16, release date: 2017-07-05, Last modification date: 2024-11-20)

Primary citation

Medina-Ramirez, M.,Garces, F.,Escolano, A.,Skog, P.,de Taeye, S.W.,Del Moral-Sanchez, I.,McGuire, A.T.,Yasmeen, A.,Behrens, A.J.,Ozorowski, G.,van den Kerkhof, T.L.G.M.,Freund, N.T.,Dosenovic, P.,Hua, Y.,Gitlin, A.D.,Cupo, A.,van der Woude, P.,Golabek, M.,Sliepen, K.,Blane, T.,Kootstra, N.,van Breemen, M.J.,Pritchard, L.K.,Stanfield, R.L.,Crispin, M.,Ward, A.B.,Stamatatos, L.,Klasse, P.J.,Moore, J.P.,Nemazee, D.,Nussenzweig, M.C.,Wilson, I.A.,Sanders, R.W.
Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo.
J. Exp. Med., 214:2573-2590, 2017

PubMed Abstract: Induction of broadly neutralizing antibodies (bNAbs) by HIV-1 envelope glycoprotein immunogens would be a major advance toward an effective vaccine. A critical step in this process is the activation of naive B cells expressing germline (gl) antibody precursors that have the potential to evolve into bNAbs. Here, we reengineered the BG505 SOSIP.664 glycoprotein to engage gl precursors of bNAbs that target either the trimer apex or the CD4-binding site. The resulting BG505 SOSIP.v4.1-GT1 trimer binds multiple bNAb gl precursors in vitro. Immunization experiments in knock-in mice expressing gl-VRC01 or gl-PGT121 show that this trimer activates B cells in vivo, resulting in the secretion of specific antibodies into the sera. A crystal structure of the gl-targeting trimer at 3.2-Å resolution in complex with neutralizing antibodies 35O22 and 9H+109L reveals a native-like conformation and the successful incorporation of design features associated with binding of multiple gl-bNAb precursors.

PubMed: 28847869
DOI: 10.1084/jem.20161160

Experimental method

X-RAY DIFFRACTION (3.202 Å)