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Yorodumi- PDB-7s8h: Structure of Lassa virus glycoprotein bound to Fab 18.5C and Fab 36.1F -
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Open data
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Basic information
| Entry | Database: PDB / ID: 7s8h | ||||||
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| Title | Structure of Lassa virus glycoprotein bound to Fab 18.5C and Fab 36.1F | ||||||
 Components | 
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 Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Lassa virus / pre-fusion glycoprotein / Fab fragment / antibody-mediated neutralization / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
| Function / homology |  Function and homology informationhost cell Golgi membrane / receptor-mediated endocytosis of virus by host cell / host cell endoplasmic reticulum membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / metal ion binding / membrane Similarity search - Function  | ||||||
| Biological species |  Lassa virus Homo sapiens (human) | ||||||
| Method |  X-RAY DIFFRACTION /  SYNCHROTRON /  MOLECULAR REPLACEMENT / Resolution: 2.7 Å  | ||||||
 Authors | Hastie, K.M. / Enriquez, A.S. | ||||||
| Funding support |   United States, 1items 
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 Citation |  Journal: Cell Rep / Year: 2022Title: Delineating the mechanism of anti-Lassa virus GPC-A neutralizing antibodies. Authors: Adrian S Enriquez / Tierra K Buck / Haoyang Li / Michael J Norris / Alex Moon-Walker / Michelle A Zandonatti / Stephanie S Harkins / James E Robinson / Luis M Branco / Robert F Garry / Erica ...Authors: Adrian S Enriquez / Tierra K Buck / Haoyang Li / Michael J Norris / Alex Moon-Walker / Michelle A Zandonatti / Stephanie S Harkins / James E Robinson / Luis M Branco / Robert F Garry / Erica Ollmann Saphire / Kathryn M Hastie / ![]() Abstract: Lassa virus (LASV) is the etiologic agent of Lassa Fever, a hemorrhagic disease that is endemic to West Africa. During LASV infection, LASV glycoprotein (GP) engages with multiple host receptors for ...Lassa virus (LASV) is the etiologic agent of Lassa Fever, a hemorrhagic disease that is endemic to West Africa. During LASV infection, LASV glycoprotein (GP) engages with multiple host receptors for cell entry. Neutralizing antibodies against GP are rare and principally target quaternary epitopes displayed only on the metastable, pre-fusion conformation of GP. Currently, the structural features of the neutralizing GPC-A antibody competition group are understudied. Structures of two GPC-A antibodies presented here demonstrate that they bind the side of the pre-fusion GP trimer, bridging the GP1 and GP2 subunits. Complementary biochemical analyses indicate that antibody 25.10C, which is broadly specific, neutralizes by inhibiting binding of the endosomal receptor LAMP1 and also by blocking membrane fusion. The other GPC-A antibody, 36.1F, which is lineage-specific, prevents LAMP1 association only. These data illuminate a site of vulnerability on LASV GP and will guide efforts to elicit broadly reactive therapeutics and vaccines.  | ||||||
| History | 
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Structure visualization
| Structure viewer | Molecule:  Molmil Jmol/JSmol | 
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Downloads & links
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Download
| PDBx/mmCIF format |  7s8h.cif.gz | 596.5 KB | Display |  PDBx/mmCIF format | 
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| PDB format |  pdb7s8h.ent.gz | 410.4 KB | Display |  PDB format | 
| PDBx/mmJSON format |  7s8h.json.gz | Tree view |  PDBx/mmJSON format | |
| Others |  Other downloads | 
-Validation report
| Summary document |  7s8h_validation.pdf.gz | 3.5 MB | Display |  wwPDB validaton report | 
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| Full document |  7s8h_full_validation.pdf.gz | 3.6 MB | Display | |
| Data in XML |  7s8h_validation.xml.gz | 44.1 KB | Display | |
| Data in CIF |  7s8h_validation.cif.gz | 61.5 KB | Display | |
| Arichive directory |  https://data.pdbj.org/pub/pdb/validation_reports/s8/7s8h ftp://data.pdbj.org/pub/pdb/validation_reports/s8/7s8h | HTTPS FTP  | 
-Related structure data
| Related structure data | ![]() 7s8gC ![]() 7tyvC ![]() 6p91S S: Starting model for refinement C: citing same article (  | 
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| Similar structure data | Similarity search - Function & homology  F&H Search | 
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Links
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Assembly
| Deposited unit | ![]() 
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| 1 | ![]() 
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| Unit cell | 
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Components
-Glycoprotein  ... , 2 types, 2 molecules Aa 
| #1: Protein |   Mass: 22927.971 Da / Num. of mol.: 1 / Mutation: G243C, Residues 256-259 mutated from RRLL to RRRR Source method: isolated from a genetically manipulated source Source: (gene. exp.)  Lassa virus / Strain: Mouse/Sierra Leone/Josiah/1976 / Gene: GPC, GP-C / Production host: ![]()  | 
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| #6: Protein |   Mass: 19117.678 Da / Num. of mol.: 1 / Mutation: E329P, M332T, I350C Source method: isolated from a genetically manipulated source Source: (gene. exp.)  Lassa virus / Strain: Mouse/Sierra Leone/Josiah/1976 / Gene: GPC, GP-C / Production host: ![]()  | 
-Antibody , 4 types, 4 molecules HLBC   
| #2: Antibody |   Mass: 24309.412 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.)  Homo sapiens (human) / Production host: ![]()  | 
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| #3: Antibody |   Mass: 23654.180 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.)  Homo sapiens (human) / Production host: ![]()  | 
| #4: Antibody |   Mass: 24174.240 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.)  Homo sapiens (human) / Production host: ![]()  | 
| #5: Antibody |   Mass: 23671.295 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.)  Homo sapiens (human) / Production host: ![]()  | 
-Sugars , 5 types, 10 molecules 
| #7: Polysaccharide |  alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...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 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #9: Polysaccharide |  2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #10: Polysaccharide | Source method: isolated from a genetically manipulated source #11: Sugar |  ChemComp-NAG /  |  | 
-Non-polymers , 1 types, 64 molecules 
| #12: Water |  ChemComp-HOH /  | 
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-Details
| Has ligand of interest | Y | 
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| Has protein modification | Y | 
-Experimental details
-Experiment
| Experiment | Method:  X-RAY DIFFRACTION / Number of used crystals: 1  | 
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Sample preparation
| Crystal | Density Matthews: 2.85 Å3/Da / Density % sol: 56.83 % | 
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| Crystal grow | Temperature: 293.15 K / Method: vapor diffusion / Details: 0.1 M Tris, pH 8.0, 1.25 M LiCl and 15% PEG 8k | 
-Data collection
| Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | 
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| Diffraction source | Source:  SYNCHROTRON / Site:  APS   / Beamline: 23-ID-D / Wavelength: 1.03319 Å | 
| Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 19, 2018 | 
| Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | 
| Radiation wavelength | Wavelength: 1.03319 Å / Relative weight: 1 | 
| Reflection | Resolution: 2.7→47.18 Å / Num. obs: 73503 / % possible obs: 99.92 % / Redundancy: 10 % / Biso Wilson estimate: 64.22 Å2 / CC1/2: 0.996 / Net I/σ(I): 9.53 | 
| Reflection shell | Resolution: 2.7→2.8 Å / Num. unique obs: 7267 / CC1/2: 0.26 | 
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Processing
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| Refinement | Method to determine structure:  MOLECULAR REPLACEMENTStarting model: 6P91 Resolution: 2.7→47.18 Å / SU ML: 0.4668 / Cross valid method: FREE R-VALUE / σ(F): 1.91 / Phase error: 29.6406 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 Details: The number of reflections in the test set (3601) was counted after merging Friedel pairs. The numbers of test set reflections in the various resolution shells were counted in the unmerged ...Details: The number of reflections in the test set (3601) was counted after merging Friedel pairs. The numbers of test set reflections in the various resolution shells were counted in the unmerged data, and thus add up to a larger number. 
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| Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Displacement parameters | Biso mean: 79.91 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Refinement step | Cycle: LAST / Resolution: 2.7→47.18 Å
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| Refine LS restraints | 
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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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About Yorodumi



Lassa virus
Homo sapiens (human)
X-RAY DIFFRACTION
United States, 1items 
Citation



PDBj





