[English] 日本語
Yorodumi- PDB-3tyg: Crystal structure of broad and potent HIV-1 neutralizing antibody... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3tyg | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Crystal structure of broad and potent HIV-1 neutralizing antibody PGT128 in complex with a glycosylated engineered gp120 outer domain with miniV3 (eODmV3) | ||||||||||||
Components |
| ||||||||||||
Keywords | IMMUNE SYSTEM / VIRAL PROTEIN / gp120 / HIV-1 / Env / Fab / HIV-1 neutralizing antibody | ||||||||||||
Function / homology | Function and homology information IgD immunoglobulin complex / IgM immunoglobulin complex / IgA immunoglobulin complex / IgE immunoglobulin complex / positive regulation of B cell activation / Synthesis and processing of ENV and VPU / evasion of host immune response / phagocytosis, recognition / Fc-gamma receptor I complex binding / CD22 mediated BCR regulation ...IgD immunoglobulin complex / IgM immunoglobulin complex / IgA immunoglobulin complex / IgE immunoglobulin complex / positive regulation of B cell activation / Synthesis and processing of ENV and VPU / evasion of host immune response / phagocytosis, recognition / Fc-gamma receptor I complex binding / CD22 mediated BCR regulation / complement-dependent cytotoxicity / Alpha-defensins / IgG immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / antibody-dependent cellular cytotoxicity / Classical antibody-mediated complement activation / Initial triggering of complement / phagocytosis, engulfment / Dectin-2 family / FCGR activation / immunoglobulin mediated immune response / Binding and entry of HIV virion / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / Scavenging of heme from plasma / immunoglobulin complex, circulating / immunoglobulin receptor binding / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / complement activation, classical pathway / host cell endosome membrane / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / actin filament organization / Regulation of Complement cascade / antigen binding / Cell surface interactions at the vascular wall / FCERI mediated MAPK activation / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / Assembly Of The HIV Virion / Budding and maturation of HIV virion / 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 / Potential therapeutics for SARS / Interleukin-4 and Interleukin-13 signaling / clathrin-dependent endocytosis of virus by host cell / adaptive immune response / blood microparticle / viral protein processing / defense response to bacterium / symbiont entry into host cell / external side of plasma membrane / fusion of virus membrane with host plasma membrane / innate immune response / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / apoptotic process / host cell plasma membrane / structural molecule activity / virion membrane / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Human immunodeficiency virus 1 Homo sapiens (human) | ||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.25 Å | ||||||||||||
Authors | Pejchal, R. / Huang, P.S. / Schief, W.R. / Stanfield, R.L. / 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 3tyg.cif.gz | 252.6 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb3tyg.ent.gz | 203.1 KB | Display | PDB format |
PDBx/mmJSON format | 3tyg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3tyg_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 3tyg_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 3tyg_validation.xml.gz | 24.7 KB | Display | |
Data in CIF | 3tyg_validation.cif.gz | 32.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ty/3tyg ftp://data.pdbj.org/pub/pdb/validation_reports/ty/3tyg | HTTPS FTP |
-Related structure data
Related structure data | 1970C 3tv3SC 3twcC S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 22019.486 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: HXB2, JR-FL / Gene: env / Plasmid: pLSEC / Cell line (production host): HEK 293S GnTI -/- / Production host: Homo sapiens (human) / References: UniProt: P04578, UniProt: Q75760 |
---|---|
#2: Antibody | Mass: 22206.559 Da / Num. of mol.: 1 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, UniProt: P0DOY3*PLUS |
#3: Antibody | Mass: 25562.686 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IGHG1 / Plasmid: pTT5 / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) / References: UniProt: P01857 |
#4: 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)]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 |
#5: 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 |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 3.23 Å3/Da / Density % sol: 61.91 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8 Details: 24% PEG 3350, 0.29M CaCl2, pH 8.0, VAPOR DIFFUSION, SITTING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 0.97945 Å |
Detector | Type: MARMOSAIC 325 mm CCD / Detector: CCD / Date: Jun 25, 2011 |
Radiation | Monochromator: Side scattering bent cube-root I-beam single crystal Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97945 Å / Relative weight: 1 |
Reflection | Resolution: 3.25→50 Å / Num. all: 14575 / Num. obs: 13988 / % possible obs: 91.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 4.1 % / Biso Wilson estimate: 50.03 Å2 / Rsym value: 0.157 / Net I/σ(I): 6.6 |
Reflection shell | Resolution: 3.25→3.37 Å / Mean I/σ(I) obs: 1.7 / Rsym value: 0.548 / % possible all: 55.6 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3TV3 Resolution: 3.25→49.7 Å / Cor.coef. Fo:Fc: 0.8398 / Cor.coef. Fo:Fc free: 0.7738 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 117.59 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.79 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.25→49.7 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 3.25→3.51 Å / Total num. of bins used: 7
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group |
|