6VPX

Nanodisc of full-length HIV-1 Envelope glycoprotein clone AMC011 in complex with one PGT151 Fab and three 10E8 Fabs

Summary for 6VPX

• Entry DOI: 10.2210/pdb6vpx/pdb
• EMDB information: 21335
• Descriptor: Envelope glycoprotein 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, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (18 entities in total)
• Functional Keywords: hiv, envelope glycoprotein, env, neutralizing antibody, nanodisc, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 17
• Total formula weight: 343307.12

Authors

Rantalainen, K.,Ward, A.B.W. (deposition date: 2020-02-04, release date: 2020-04-22, Last modification date: 2024-11-20)

Primary citation

Rantalainen, K.,Berndsen, Z.T.,Antanasijevic, A.,Schiffner, T.,Zhang, X.,Lee, W.H.,Torres, J.L.,Zhang, L.,Irimia, A.,Copps, J.,Zhou, K.H.,Kwon, Y.D.,Law, W.H.,Schramm, C.A.,Verardi, R.,Krebs, S.J.,Kwong, P.D.,Doria-Rose, N.A.,Wilson, I.A.,Zwick, M.B.,Yates 3rd, J.R.,Schief, W.R.,Ward, A.B.
HIV-1 Envelope and MPER Antibody Structures in Lipid Assemblies.
Cell Rep, 31:107583-107583, 2020

PubMed Abstract: Structural and functional studies of HIV envelope glycoprotein (Env) as a transmembrane protein have long been complicated by challenges associated with inherent flexibility of the molecule and the membrane-embedded hydrophobic regions. Here, we present approaches for incorporating full-length, wild-type HIV-1 Env, as well as C-terminally truncated and stabilized versions, into lipid assemblies, providing a modular platform for Env structural studies by single particle electron microscopy. We reconstitute a full-length Env clone into a nanodisc, complex it with a membrane-proximal external region (MPER) targeting antibody 10E8, and structurally define the full quaternary epitope of 10E8 consisting of lipid, MPER, and ectodomain contacts. By aligning this and other Env-MPER antibody complex reconstructions with the lipid bilayer, we observe evidence of Env tilting as part of the neutralization mechanism for MPER-targeting antibodies. We also adapt the platform toward vaccine design purposes by introducing stabilizing mutations that allow purification of unliganded Env with a peptidisc scaffold.

PubMed: 32348769
DOI: 10.1016/j.celrep.2020.107583

Experimental method

ELECTRON MICROSCOPY (5 Å)