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Structure of HIV-1 gp41 with its membrane anchors targeted by neutralizing antibodies
Copyright policy )EC| EAVI2020 ,
ANR| CBH-EUR-GS
Christophe Caillat; Delphine Guilligay; Johana Torralba; Nikolas Friedrich; Jose L Nieva; Alexandra Trkola; Christophe J Chipot; +2 Authors
Christophe Caillat; Delphine Guilligay; Johana Torralba; Nikolas Friedrich; Jose L Nieva; Alexandra Trkola; Christophe J Chipot; François L Dehez; Winfried Weissenhorn;
Structure of HIV-1 gp41 with its membrane anchors targeted by neutralizing antibodies
AbstractThe HIV-1 gp120/gp41 trimer undergoes a series of conformational changes in order to catalyze gp41-induced fusion of viral and cellular membranes. Here, we present the crystal structure of gp41 locked in a fusion intermediate state by an MPER-specific neutralizing antibody. The structure illustrates the conformational plasticity of the six membrane anchors arranged asymmetrically with the fusion peptides and the transmembrane regions pointing into different directions. Hinge regions located adjacent to the fusion peptide and the transmembrane region facilitate the conformational flexibility that allows high affinity binding of broadly neutralizing anti-MPER antibodies. Molecular dynamics simulation of the MPER Ab-induced gp41 conformation reveals the transition into the final post-fusion conformation with the central fusion peptides forming a hydrophobic core with flanking transmembrane regions. This, thus, suggests that MPER-specific broadly neutralizing antibodies can block final steps of refolding of the fusion peptide and the transmembrane region, which is required for completing membrane fusion.
Switzerland, France, Spain, France, Spain
- French National Centre for Scientific Research France
- University of Lorraine France
- Stanford University United States
- Commissariat à l’Energie Atomique et aux Energies Alternatives France
- Université de Lorraine France
10028 Institute of Medical Virology, Protein Folding, Protein Conformation, membrane fusion, Lipid Bilayers, HIV Antibodies, Membrane Fusion, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Antibody Specificity, 2400 General Immunology and Microbiology, Biology (General), [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Microbiology and Infectious Disease, Protein Stability, Q, R, 2800 General Neuroscience, Molecular biophysics, gp41, HIV Envelope Protein gp41, Virus, transmembrane, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Infectious diseases, crystal structure of gp41 locked, Gp41, Structural biology, Protein Binding, 570, viral and cellular membranes, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], QH301-705.5, Science, Membrane fusion, 610 Medicine & health, Molecular Dynamics Simulation, Microbiology, Structure-Activity Relationship, 4E10, 1300 General Biochemistry, Genetics and Molecular Biology, 2H10, Humans, neutralizing antibodies, Molecular Biology/Structural Biology [q-bio.BM], Single-Domain Antibodies, 540, hydrophobic core, HEK293 Cells, gp41-induced fusion, HIV-1, 570 Life sciences; biology, fusion peptide, LN01, Binding Sites, Antibody, Broadly Neutralizing Antibodies
10028 Institute of Medical Virology, Protein Folding, Protein Conformation, membrane fusion, Lipid Bilayers, HIV Antibodies, Membrane Fusion, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Antibody Specificity, 2400 General Immunology and Microbiology, Biology (General), [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Microbiology and Infectious Disease, Protein Stability, Q, R, 2800 General Neuroscience, Molecular biophysics, gp41, HIV Envelope Protein gp41, Virus, transmembrane, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Infectious diseases, crystal structure of gp41 locked, Gp41, Structural biology, Protein Binding, 570, viral and cellular membranes, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], QH301-705.5, Science, Membrane fusion, 610 Medicine & health, Molecular Dynamics Simulation, Microbiology, Structure-Activity Relationship, 4E10, 1300 General Biochemistry, Genetics and Molecular Biology, 2H10, Humans, neutralizing antibodies, Molecular Biology/Structural Biology [q-bio.BM], Single-Domain Antibodies, 540, hydrophobic core, HEK293 Cells, gp41-induced fusion, HIV-1, 570 Life sciences; biology, fusion peptide, LN01, Binding Sites, Antibody, Broadly Neutralizing Antibodies
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).17 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10% views 58 downloads 59 - 58views59downloads
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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Citations provided by BIP!popularityPopularity provided by BIP!
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Influence provided by BIP!impulseImpulse provided by BIP!
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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