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Yorodumi- PDB-6okp: B41 SOSIP.664 in complex with the silent-face antibody SF12 and V... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6okp | |||||||||
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Title | B41 SOSIP.664 in complex with the silent-face antibody SF12 and V3-targeting antibody 10-1074 | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 broadly-neutralizing antibody / Env trimer structure / silent face / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information IgD immunoglobulin complex / IgM immunoglobulin complex / IgA immunoglobulin complex / IgE immunoglobulin complex / CD22 mediated BCR regulation / IgG immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement / FCGR activation ...IgD immunoglobulin complex / IgM immunoglobulin complex / IgA immunoglobulin complex / IgE immunoglobulin complex / CD22 mediated BCR regulation / IgG immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement / FCGR activation / immunoglobulin mediated immune response / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / Scavenging of heme from plasma / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / immunoglobulin complex, circulating / immunoglobulin receptor binding / positive regulation of establishment of T cell polarity / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / host cell endosome membrane / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / complement activation, classical pathway / Regulation of Complement cascade / Cell surface interactions at the vascular wall / FCERI mediated MAPK activation / antigen binding / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / Regulation of actin dynamics for phagocytic cup formation / FCERI mediated NF-kB activation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / antibacterial humoral response / clathrin-dependent endocytosis of virus by host cell / adaptive immune response / Potential therapeutics for SARS / blood microparticle / viral protein processing / immune response / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / apoptotic process / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / extracellular space / extracellular exosome / extracellular region / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.28 Å | |||||||||
Authors | Barnes, C.O. / Bjorkman, P.J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Immunity / Year: 2019 Title: Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope. Authors: Till Schoofs / Christopher O Barnes / Nina Suh-Toma / Jovana Golijanin / Philipp Schommers / Henning Gruell / Anthony P West / Franziska Bach / Yu Erica Lee / Lilian Nogueira / Ivelin S ...Authors: Till Schoofs / Christopher O Barnes / Nina Suh-Toma / Jovana Golijanin / Philipp Schommers / Henning Gruell / Anthony P West / Franziska Bach / Yu Erica Lee / Lilian Nogueira / Ivelin S Georgiev / Robert T Bailer / Julie Czartoski / John R Mascola / Michael S Seaman / M Juliana McElrath / Nicole A Doria-Rose / Florian Klein / Michel C Nussenzweig / Pamela J Bjorkman / Abstract: Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization ...Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3Å cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448 glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6okp.cif.gz | 521.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6okp.ent.gz | 433.5 KB | Display | PDB format |
PDBx/mmJSON format | 6okp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6okp_validation.pdf.gz | 3.4 MB | Display | wwPDB validaton report |
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Full document | 6okp_full_validation.pdf.gz | 3.4 MB | Display | |
Data in XML | 6okp_validation.xml.gz | 86.3 KB | Display | |
Data in CIF | 6okp_validation.cif.gz | 127.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ok/6okp ftp://data.pdbj.org/pub/pdb/validation_reports/ok/6okp | HTTPS FTP |
-Related structure data
Related structure data | 20100MC 6okqC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Envelope glycoprotein ... , 2 types, 6 molecules ABCDEF
#1: Protein | Mass: 17357.824 Da / Num. of mol.: 3 / Fragment: UNP residues 516-668 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: B41 / Gene: env / Variant: SOSIP.664 v4.2 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: B3UEZ6 #2: Protein | Mass: 57702.469 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: B41 / Cell: B-Cell / Gene: env / Variant: SOSIP.664 v4.2 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: B3UES2 |
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-Protein , 1 types, 1 molecules K
#3: Protein | Mass: 26490.568 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell: B-Cell / Plasmid: p3BNC / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: S6B291 |
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-Antibody , 3 types, 7 molecules LMOQNPR
#4: Antibody | Mass: 23180.760 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell: B-Cell / Plasmid: p3BNC / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: Q8N5F4 | ||
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#5: Antibody | Mass: 26045.205 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell: B-Cell / Plasmid: p3BNC / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: S6B291 #6: Antibody | Mass: 23236.971 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: p3BNC / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: P01834 |
-Sugars , 8 types, 64 molecules
#7: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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 Source method: isolated from a genetically manipulated source | ||||||||||||
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#8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[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 Source method: isolated from a genetically manipulated source #10: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #11: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #12: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[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 | Source method: isolated from a genetically manipulated source #13: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D- ...alpha-D-mannopyranose-(1-2)-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 | Source method: isolated from a genetically manipulated source #14: Sugar | ChemComp-NAG / |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight | Value: 0.54 MDa / Experimental value: NO | |||||||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | |||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R2/2 | |||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 K Details: 0 blot force, 3 second blot time, 3 uL sample added to freshly glow-discharged grids |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 8 sec. / Electron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2732 |
Image scans | Movie frames/image: 40 / Used frames/image: 1-40 |
-Processing
Software | Name: PHENIX / Version: 1.14_3219: / Classification: refinement | ||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 676161 Details: manual picking followed by template-based autopicking | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.28 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 301920 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL / Target criteria: Correlation coefficient | ||||||||||||||||||||||||||||||||||||
Atomic model building |
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Refinement | Highest resolution: 3.28 Å | ||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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