+Open data
-Basic information
Entry | Database: PDB / ID: 6pz8 | |||||||||
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Title | MERS S0 trimer in complex with variable domain of antibody G2 | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / MERS-CoV / coronavirus / DPP4 / receptor-binding / membrane fusion / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information : / membrane => GO:0016020 / endocytosis involved in viral entry into host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane ...: / membrane => GO:0016020 / endocytosis involved in viral entry into host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | Middle East respiratory syndrome-related coronavirus Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.19 Å | |||||||||
Authors | Bowman, C.A. / Pallesen, J. / Ward, A.B. | |||||||||
Funding support | United States, 1items
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Citation | Journal: Cell Rep / Year: 2019 Title: Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD. Authors: Nianshuang Wang / Osnat Rosen / Lingshu Wang / Hannah L Turner / Laura J Stevens / Kizzmekia S Corbett / Charles A Bowman / Jesper Pallesen / Wei Shi / Yi Zhang / Kwanyee Leung / Robert N ...Authors: Nianshuang Wang / Osnat Rosen / Lingshu Wang / Hannah L Turner / Laura J Stevens / Kizzmekia S Corbett / Charles A Bowman / Jesper Pallesen / Wei Shi / Yi Zhang / Kwanyee Leung / Robert N Kirchdoerfer / Michelle M Becker / Mark R Denison / James D Chappell / Andrew B Ward / Barney S Graham / Jason S McLellan / Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the ...Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6pz8.cif.gz | 723.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6pz8.ent.gz | 579.7 KB | Display | PDB format |
PDBx/mmJSON format | 6pz8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6pz8_validation.pdf.gz | 3 MB | Display | wwPDB validaton report |
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Full document | 6pz8_full_validation.pdf.gz | 3 MB | Display | |
Data in XML | 6pz8_validation.xml.gz | 108.4 KB | Display | |
Data in CIF | 6pz8_validation.cif.gz | 164.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pz/6pz8 ftp://data.pdbj.org/pub/pdb/validation_reports/pz/6pz8 | HTTPS FTP |
-Related structure data
Related structure data | 20527MC 0486C 6pxgC 6pxhC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 3 types, 9 molecules AEIBJFHCD
#1: Protein | Mass: 51301.617 Da / Num. of mol.: 3 / Fragment: S2 C-terminal domain (UNP residues 753-1223) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Middle East respiratory syndrome-related coronavirus Production host: Homo sapiens (human) / References: UniProt: W5ZZF5, UniProt: K9N5Q8*PLUS #2: Protein | Mass: 80409.109 Da / Num. of mol.: 3 / Fragment: S0 N-terminal domain (UNP residues 18-743) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Middle East respiratory syndrome-related coronavirus Production host: Homo sapiens (human) / References: UniProt: W6A090, UniProt: K9N5Q8*PLUS #3: Protein | Mass: 24275.059 Da / Num. of mol.: 3 / Fragment: variable domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) |
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-Antibody , 1 types, 3 molecules LGK
#4: Antibody | Mass: 23861.293 Da / Num. of mol.: 3 / Fragment: variable domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) |
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-Sugars , 4 types, 42 molecules
#5: 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 #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Sugar | ChemComp-NAG / |
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-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 |
-Sample preparation
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 77 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 418781 | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.19 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 12386 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Details: Model was not refined. | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 5W9I |