+Open data
-Basic information
Entry | Database: PDB / ID: 4m5y | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of broadly neutralizing Fab 5J8 | ||||||
Components |
| ||||||
Keywords | IMMUNE SYSTEM / immunoglobulin fold / fragment antigen binding / influenza hemagglutinin receptor binding site | ||||||
Function / homology | Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta / DI(HYDROXYETHYL)ETHER Function and homology information | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.55 Å | ||||||
Authors | Lee, P.S. / Wilson, I.A. | ||||||
Citation | Journal: J Virol / Year: 2013 Title: Antibody recognition of the pandemic H1N1 Influenza virus hemagglutinin receptor binding site. Authors: Minsun Hong / Peter S Lee / Ryan M B Hoffman / Xueyong Zhu / Jens C Krause / Nick S Laursen / Sung-Il Yoon / Langzhou Song / Lynda Tussey / James E Crowe / Andrew B Ward / Ian A Wilson Abstract: Influenza virus is a global health concern due to its unpredictable pandemic potential. This potential threat was realized in 2009 when an H1N1 virus emerged that resembled the 1918 virus in ...Influenza virus is a global health concern due to its unpredictable pandemic potential. This potential threat was realized in 2009 when an H1N1 virus emerged that resembled the 1918 virus in antigenicity but fortunately was not nearly as deadly. 5J8 is a human antibody that potently neutralizes a broad spectrum of H1N1 viruses, including the 1918 and 2009 pandemic viruses. Here, we present the crystal structure of 5J8 Fab in complex with a bacterially expressed and refolded globular head domain from the hemagglutinin (HA) of the A/California/07/2009 (H1N1) pandemic virus. 5J8 recognizes a conserved epitope in and around the receptor binding site (RBS), and its HCDR3 closely mimics interactions of the sialic acid receptor. Electron microscopy (EM) reconstructions of 5J8 Fab in complex with an HA trimer from a 1986 H1 strain and with an engineered stabilized HA trimer from the 2009 H1 pandemic virus showed a similar mode of binding. As for other characterized RBS-targeted antibodies, 5J8 uses avidity to extend its breadth and affinity against divergent H1 strains. 5J8 selectively interacts with HA insertion residue 133a, which is conserved in pandemic H1 strains and has precluded binding of other RBS-targeted antibodies. Thus, the RBS of divergent HAs is targeted by 5J8 and adds to the growing arsenal of common recognition motifs for design of therapeutics and vaccines. Moreover, consistent with previous studies, the bacterially expressed H1 HA properly refolds, retaining its antigenic structure, and presents a low-cost and rapid alternative for engineering and manufacturing candidate flu vaccines. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4m5y.cif.gz | 360.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4m5y.ent.gz | 292.8 KB | Display | PDB format |
PDBx/mmJSON format | 4m5y.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4m5y_validation.pdf.gz | 477.4 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 4m5y_full_validation.pdf.gz | 487.3 KB | Display | |
Data in XML | 4m5y_validation.xml.gz | 42.8 KB | Display | |
Data in CIF | 4m5y_validation.cif.gz | 62.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m5/4m5y ftp://data.pdbj.org/pub/pdb/validation_reports/m5/4m5y | HTTPS FTP |
-Related structure data
Related structure data | 5731C 5733C 4m4yC 4m5zC 3mlyS C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
2 |
| ||||||||
Unit cell |
|
-Components
#1: Antibody | Mass: 25088.070 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Trichoplusia ni (cabbage looper) #2: Antibody | Mass: 22760.098 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Trichoplusia ni (cabbage looper) #3: Chemical | ChemComp-PEG / #4: Chemical | ChemComp-PG4 / | #5: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 3.41 Å3/Da / Density % sol: 63.98 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8 Details: 0.2 M calcium acetate, 11% PEG3350, pH 8, VAPOR DIFFUSION, SITTING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 77 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1.0332 Å |
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Nov 17, 2012 |
Radiation | Monochromator: Double crystal cryo-cooled Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 1.55→50 Å / Num. all: 190412 / Num. obs: 183997 / % possible obs: 96.9 % / Observed criterion σ(I): -3 / Redundancy: 7.3 % / Biso Wilson estimate: 20.1 Å2 / Rmerge(I) obs: 0.046 / Rsym value: 0.046 / Net I/σ(I): 21.9 |
Reflection shell | Resolution: 1.55→1.57 Å / Redundancy: 5.6 % / Rmerge(I) obs: 0.91 / Mean I/σ(I) obs: 1.8 / Num. unique all: 6687 / Rsym value: 0.91 / % possible all: 72.5 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3MLY CHAINS H AND L Resolution: 1.55→49.151 Å / SU ML: 0.13 / σ(F): 2 / Phase error: 19.02 / Stereochemistry target values: ML
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.55→49.151 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group |
|