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Yorodumi- PDB-3tv3: Crystal structure of broad and potent HIV-1 neutralizing antibody... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3tv3 | ||||||||||||
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Title | Crystal structure of broad and potent HIV-1 neutralizing antibody PGT128 in complex with Man9 | ||||||||||||
Components |
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Keywords | IMMUNE SYSTEM / Fab / HIV-1 neutralizing antibody / gp120 | ||||||||||||
Function / homology | Function and homology information IgD immunoglobulin complex / IgM immunoglobulin complex / IgA immunoglobulin complex / IgE immunoglobulin complex / positive regulation of B cell activation / phagocytosis, recognition / CD22 mediated BCR regulation / complement-dependent cytotoxicity / antibody-dependent cellular cytotoxicity / Fc epsilon receptor (FCERI) signaling ...IgD immunoglobulin complex / IgM immunoglobulin complex / IgA immunoglobulin complex / IgE immunoglobulin complex / positive regulation of B cell activation / phagocytosis, recognition / CD22 mediated BCR regulation / complement-dependent cytotoxicity / antibody-dependent cellular cytotoxicity / Fc epsilon receptor (FCERI) signaling / Fc-gamma receptor I complex binding / Classical antibody-mediated complement activation / phagocytosis, engulfment / Initial triggering of complement / immunoglobulin complex, circulating / IgG immunoglobulin complex / immunoglobulin receptor binding / FCGR activation / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / Scavenging of heme from plasma / complement activation, classical pathway / antigen binding / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of Complement cascade / Cell surface interactions at the vascular wall / FCGR3A-mediated phagocytosis / FCERI mediated MAPK activation / 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 / blood microparticle / Interleukin-4 and Interleukin-13 signaling / adaptive immune response / defense response to bacterium / external side of plasma membrane / innate immune response / extracellular space / extracellular exosome / extracellular region / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.29 Å | ||||||||||||
Authors | Pejchal, R. / Wilson, I.A. | ||||||||||||
Citation | Journal: Science / Year: 2011 Title: A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Authors: Robert Pejchal / Katie J Doores / Laura M Walker / Reza Khayat / Po-Ssu Huang / Sheng-Kai Wang / Robyn L Stanfield / Jean-Philippe Julien / Alejandra Ramos / Max Crispin / Rafael Depetris / ...Authors: Robert Pejchal / Katie J Doores / Laura M Walker / Reza Khayat / Po-Ssu Huang / Sheng-Kai Wang / Robyn L Stanfield / Jean-Philippe Julien / Alejandra Ramos / Max Crispin / Rafael Depetris / Umesh Katpally / Andre Marozsan / Albert Cupo / Sebastien Maloveste / Yan Liu / Ryan McBride / Yukishige Ito / Rogier W Sanders / Cassandra Ogohara / James C Paulson / Ten Feizi / Christopher N Scanlan / Chi-Huey Wong / John P Moore / William C Olson / Andrew B Ward / Pascal Poignard / William R Schief / Dennis R Burton / Ian A Wilson / Abstract: The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to ...The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of antigen-binding fragments (Fabs) PGT 127 and 128 with Man(9) at 1.65 and 1.29 angstrom resolution, respectively, and glycan binding data delineate a specific high mannose-binding site. Fab PGT 128 complexed with a fully glycosylated gp120 outer domain at 3.25 angstroms reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short β-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificity. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 immunoglobulin Gs may be mediated by cross-linking Env trimers on the viral surface. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3tv3.cif.gz | 261.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3tv3.ent.gz | 224.7 KB | Display | PDB format |
PDBx/mmJSON format | 3tv3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tv/3tv3 ftp://data.pdbj.org/pub/pdb/validation_reports/tv/3tv3 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Antibody , 2 types, 2 molecules LH
#1: Antibody | Mass: 22223.588 Da / Num. of mol.: 1 / Fragment: PGT128 light chain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IGLC2 / Plasmid: pTT5 / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) / References: UniProt: P0CG05 |
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#2: Antibody | Mass: 25562.686 Da / Num. of mol.: 1 / Fragment: PGT128 heavy chain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: pTT5 / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) / References: UniProt: P01857 |
-Sugars , 1 types, 1 molecules
#3: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose Source method: isolated from a genetically manipulated source |
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-Non-polymers , 4 types, 312 molecules
#4: Chemical | ChemComp-GOL / #5: Chemical | ChemComp-AML / | #6: Chemical | ChemComp-EPE / | #7: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.91 Å3/Da / Density % sol: 57.69 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 11% PEG 4000, 0.1M HEPES, 10% isopropanol, 6.5mM Man9, pH 7.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.9795 Å |
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: May 13, 2011 |
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: 1.29→25 Å / Num. all: 139537 / Num. obs: 139361 / % possible obs: 99.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 6.5 % / Biso Wilson estimate: 14 Å2 / Rsym value: 0.077 / Net I/σ(I): 13.1 |
Reflection shell | Resolution: 1.29→1.32 Å / Redundancy: 6.4 % / Mean I/σ(I) obs: 3.27 / Num. unique all: 10219 / Rsym value: 0.546 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.29→24.899 Å / SU ML: 0.15 / Isotropic thermal model: ANISOTROPIC / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 14.27 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.6 Å / VDW probe radii: 0.9 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 41.437 Å2 / ksol: 0.416 e/Å3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 20.6 Å2
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Refine analyze | Luzzati coordinate error obs: 0.15 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.29→24.899 Å
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Refine LS restraints |
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LS refinement shell |
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