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- PDB-4nm8: Crystal structure of broadly neutralizing antibody CR8043 bound t... -
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Open data
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Basic information
Entry | Database: PDB / ID: 4nm8 | |||||||||
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Title | Crystal structure of broadly neutralizing antibody CR8043 bound to H3 influenza hemagglutinin | |||||||||
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![]() | viral protein/immune system / Viral fusion protein / immunoglobulin / virus attachment and entry / immune recognition / viral protein-immune system complex / Immunoglobulin' | |||||||||
Function / homology | ![]() IgD immunoglobulin complex / IgM immunoglobulin complex / IgA immunoglobulin complex / IgE immunoglobulin complex / CD22 mediated BCR regulation / immunoglobulin complex / IgG immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement ...IgD immunoglobulin complex / IgM immunoglobulin complex / IgA immunoglobulin complex / IgE immunoglobulin complex / CD22 mediated BCR regulation / immunoglobulin complex / 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 / immunoglobulin complex, circulating / immunoglobulin receptor binding / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / viral budding from plasma 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 / FCGR3A-mediated phagocytosis / antigen binding / 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 / host cell surface receptor binding / immune response / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / extracellular space / extracellular exosome / extracellular region / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Lee, P.S. / Wilson, I.A. | |||||||||
![]() | ![]() Title: A common solution to group 2 influenza virus neutralization. Authors: Robert H E Friesen / Peter S Lee / Esther J M Stoop / Ryan M B Hoffman / Damian C Ekiert / Gira Bhabha / Wenli Yu / Jarek Juraszek / Wouter Koudstaal / Mandy Jongeneelen / Hans J W M Korse / ...Authors: Robert H E Friesen / Peter S Lee / Esther J M Stoop / Ryan M B Hoffman / Damian C Ekiert / Gira Bhabha / Wenli Yu / Jarek Juraszek / Wouter Koudstaal / Mandy Jongeneelen / Hans J W M Korse / Carla Ophorst / Els C M Brinkman-van der Linden / Mark Throsby / Mark J Kwakkenbos / Arjen Q Bakker / Tim Beaumont / Hergen Spits / Ted Kwaks / Ronald Vogels / Andrew B Ward / Jaap Goudsmit / Ian A Wilson / ![]() Abstract: The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the ...The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the design of universal influenza vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043, which was derived from a different germ-line gene encoding a highly divergent amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10 viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7 viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an alternative angle of approach and a distinct set of interactions. The identification of another antibody against the group 2 stem epitope suggests that this conserved site of vulnerability has great potential for design of therapeutics and vaccines. | |||||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1 MB | Display | ![]() |
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PDB format | ![]() | 903.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 2 MB | Display | ![]() |
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Full document | ![]() | 2 MB | Display | |
Data in XML | ![]() | 93.6 KB | Display | |
Data in CIF | ![]() | 125.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5793C ![]() 5794C ![]() 4nm4SC ![]() 4fnkS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
-Hemagglutinin ... , 2 types, 6 molecules ACEBDF
#1: Protein | Mass: 35506.949 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Strain: A/Hong Kong/1/1968 H3N2 / Gene: HA / Production host: ![]() #2: Protein | Mass: 20197.312 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Strain: A/Hong Kong/1/1968 H3N2 / Gene: HA / Production host: ![]() |
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-Antibody , 2 types, 6 molecules LMNHIJ
#3: Antibody | Mass: 24228.805 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Antibody | Mass: 24753.713 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 2 types, 14 molecules ![](data/chem/img/NAG.gif)
#5: 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 #6: Sugar | ChemComp-NAG / |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.39 Å3/Da / Density % sol: 63.73 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 5.5 Details: 2.2 M ammonium sulfate, 0.1 M sodium acetate pH 5.5, 3% PEG 400, VAPOR DIFFUSION, SITTING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 77 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Mar 22, 2012 |
Radiation | Monochromator: Liquid nitrogen-cooled double crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 4→50 Å / Num. all: 34622 / Num. obs: 34622 / % possible obs: 97.7 % / Observed criterion σ(I): -3 / Redundancy: 6.8 % / Biso Wilson estimate: 92.5 Å2 / Rmerge(I) obs: 0.201 / Rsym value: 0.201 / Net I/σ(I): 6.4 |
Reflection shell | Resolution: 4→4.2 Å / Redundancy: 6.5 % / Rmerge(I) obs: 0.826 / Mean I/σ(I) obs: 2.2 / Num. unique all: 4271 / Rsym value: 0.826 / % possible all: 90.8 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: PDB ENTRY 4FNK, 4NM4 Resolution: 4.0041→43.821 Å / SU ML: 0.55 / σ(F): 1.99 / Phase error: 30.61 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 4.0041→43.821 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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