5W6D

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

5W6D の概要

• エントリーDOI: 10.2210/pdb5w6d/pdb
• 分子名称: 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)
• 機能のキーワード: hiv-1 broadly neutralizing antibody, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human immunodeficiency virus 1 (HIV-1); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 176226.50

構造登録者

Garces, F.,Stanfield, R.L.,Wilson, I.A. (登録日: 2017-06-16, 公開日: 2017-07-05, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.202 Å)