6CUE

Cryo-EM structure at 4.0 A resolution of vaccine-elicited antibody vFP7.04 in complex with HIV-1 Env BG505 DS-SOSIP, and antibodies VRC03 and PGT122

This is a non-PDB format compatible entry.

Summary for 6CUE

• Entry DOI: 10.2210/pdb6cue/pdb
• EMDB information: 7621
• Descriptor: Envelope glycoprotein gp120, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 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, ... (14 entities in total)
• Functional Keywords: hiv-1 env, bg505 sosip, fusion peptide, vrc03, pgt122, vfp7.04, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 24
• Total formula weight: 466613.36

Authors

Acharya, P.,Carragher, B.,Potter, C.S.,Kwong, P.D. (deposition date: 2018-03-26, release date: 2018-07-11, Last modification date: 2024-10-16)

Primary citation

Dingens, A.S.,Acharya, P.,Haddox, H.K.,Rawi, R.,Xu, K.,Chuang, G.Y.,Wei, H.,Zhang, B.,Mascola, J.R.,Carragher, B.,Potter, C.S.,Overbaugh, J.,Kwong, P.D.,Bloom, J.D.
Complete functional mapping of infection- and vaccine-elicited antibodies against the fusion peptide of HIV.
PLoS Pathog., 14:e1007159-e1007159, 2018

PubMed Abstract: Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env's fusion peptide.

PubMed: 29975771
DOI: 10.1371/journal.ppat.1007159

Experimental method

ELECTRON MICROSCOPY (4 Å)