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Open data
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Basic information
Entry | Database: PDB / ID: 8ejj | |||||||||
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Title | Lassa virus glycoprotein complex (Josiah) bound to S370.7 Fab | |||||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / glycoprotein complex / Lassa mammarenavirus / LASV / GPC / immune system / viral fusion protein / Lassa virus / lineage IV / Josiah / S370.7 / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() host 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 / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.22 Å | |||||||||
![]() | Perrett, H.R. / Ward, A.B. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies. Authors: Hailee R Perrett / Philip J M Brouwer / Jonathan Hurtado / Maddy L Newby / Lin Liu / Helena Müller-Kräuter / Sarah Müller Aguirre / Judith A Burger / Joey H Bouhuijs / Grace Gibson / ...Authors: Hailee R Perrett / Philip J M Brouwer / Jonathan Hurtado / Maddy L Newby / Lin Liu / Helena Müller-Kräuter / Sarah Müller Aguirre / Judith A Burger / Joey H Bouhuijs / Grace Gibson / Terrence Messmer / John S Schieffelin / Aleksandar Antanasijevic / Geert-Jan Boons / Thomas Strecker / Max Crispin / Rogier W Sanders / Bryan Briney / Andrew B Ward / ![]() ![]() ![]() ![]() Abstract: Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. ...Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 370.5 KB | Display | ![]() |
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PDB format | ![]() | 306.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 28184MC ![]() 8ejdC ![]() 8ejeC ![]() 8ejfC ![]() 8ejgC ![]() 8ejhC ![]() 8ejiC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Glycoprotein ... , 2 types, 6 molecules ABCabc
#1: Protein | Mass: 22199.053 Da / Num. of mol.: 3 / Mutation: H207C Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Protein | Mass: 19146.824 Da / Num. of mol.: 3 / Mutation: L257R, L258R, E328P, G359C Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Antibody , 2 types, 6 molecules HIhJLl
#2: Antibody | Mass: 14109.716 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Antibody | Mass: 11517.611 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 8 types, 34 molecules ![](data/chem/img/NAG.gif)
![](data/chem/img/MAN.gif)
![](data/chem/img/MAN.gif)
#5: 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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#6: 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 #7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Polysaccharide | Source method: isolated from a genetically manipulated source #10: Polysaccharide | Source method: isolated from a genetically manipulated source #11: Sugar | ChemComp-NAG / #12: Sugar | ChemComp-MAN / | |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Lassa mammarenavirus GPC / Type: COMPLEX Details: GPC protein codon-optimized and expressed in HEK 293F cells using covalently-linked I53-50A trimerization scaffold bound to S370.7 Fab Entity ID: #1-#4 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 0.425 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Details of virus | Empty: NO / Enveloped: YES / Isolate: STRAIN / Type: VIRION |
Natural host | Organism: Mastomys natalensis |
Buffer solution | pH: 7.4 / Details: TBS |
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K Details: Wait time 10 s; blotting time varied between 3-7 s; blotting force of 0 |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 700 nm |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50.11 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.22 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 96449 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7SGD Accession code: 7SGD / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||
Refine LS restraints |
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