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Yorodumi- PDB-8sqn: CryoEM structure of Western equine encephalitis virus VLP in comp... -
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-Basic information
Entry | Database: PDB / ID: 8sqn | ||||||
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Title | CryoEM structure of Western equine encephalitis virus VLP in complex with the chimeric Du-D1-Mo-D2 MXRA8 receptor | ||||||
Components |
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Keywords | VIRAL PROTEIN/SIGNALING PROTEIN / WEEV / MXRA8 / Receptor / Alphavirus / Avian / VLP / Structural Genomics / PSI-2 / Protein Structure Initiative / Center for Structural Genomics of Infectious Diseases / CSGID / VIRAL PROTEIN-SIGNALING PROTEIN complex | ||||||
Function / homology | Function and homology information T=4 icosahedral viral capsid / host cell cytoplasm / symbiont entry into host cell / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / proteolysis ...T=4 icosahedral viral capsid / host cell cytoplasm / symbiont entry into host cell / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / proteolysis / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Anas platyrhynchos (mallard) Western equine encephalitis virus | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.89 Å | ||||||
Authors | Zimmerman, M.I. / Fremont, D.H. / Center for Structural Genomics of Infectious Diseases (CSGID) / Center for Structural Biology of Infectious Diseases (CSBID) | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell / Year: 2023 Title: Vertebrate-class-specific binding modes of the alphavirus receptor MXRA8. Authors: Ofer Zimmerman / Maxwell I Zimmerman / Saravanan Raju / Christopher A Nelson / John M Errico / Emily A Madden / Autumn C Holmes / Ahmed O Hassan / Laura A VanBlargan / Arthur S Kim / Lucas J ...Authors: Ofer Zimmerman / Maxwell I Zimmerman / Saravanan Raju / Christopher A Nelson / John M Errico / Emily A Madden / Autumn C Holmes / Ahmed O Hassan / Laura A VanBlargan / Arthur S Kim / Lucas J Adams / Katherine Basore / Bradley M Whitener / Sathvik Palakurty / Hannah G Davis-Adams / Chengqun Sun / Theron Gilliland / James T Earnest / Hongming Ma / Gregory D Ebel / Christian Zmasek / Richard H Scheuermann / William B Klimstra / Daved H Fremont / Michael S Diamond / Abstract: MXRA8 is a receptor for chikungunya (CHIKV) and other arthritogenic alphaviruses with mammalian hosts. However, mammalian MXRA8 does not bind to alphaviruses that infect humans and have avian ...MXRA8 is a receptor for chikungunya (CHIKV) and other arthritogenic alphaviruses with mammalian hosts. However, mammalian MXRA8 does not bind to alphaviruses that infect humans and have avian reservoirs. Here, we show that avian, but not mammalian, MXRA8 can act as a receptor for Sindbis, western equine encephalitis (WEEV), and related alphaviruses with avian reservoirs. Structural analysis of duck MXRA8 complexed with WEEV reveals an inverted binding mode compared with mammalian MXRA8 bound to CHIKV. Whereas both domains of mammalian MXRA8 bind CHIKV E1 and E2, only domain 1 of avian MXRA8 engages WEEV E1, and no appreciable contacts are made with WEEV E2. Using these results, we generated a chimeric avian-mammalian MXRA8 decoy-receptor that neutralizes infection of multiple alphaviruses from distinct antigenic groups in vitro and in vivo. Thus, different alphaviruses can bind MXRA8 encoded by different vertebrate classes with distinct engagement modes, which enables development of broad-spectrum inhibitors. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8sqn.cif.gz | 1.1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8sqn.ent.gz | 971.7 KB | Display | PDB format |
PDBx/mmJSON format | 8sqn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sq/8sqn ftp://data.pdbj.org/pub/pdb/validation_reports/sq/8sqn | HTTPS FTP |
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-Related structure data
Related structure data | 40711MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 30539.193 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Anas platyrhynchos (mallard) / Production host: Homo sapiens (human) | ||||||
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#2: Protein | Mass: 47188.562 Da / Num. of mol.: 4 / Fragment: UNP residues 798-1235 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Western equine encephalitis virus / Production host: Homo sapiens (human) / References: UniProt: Q1W679 #3: Protein | Mass: 46171.617 Da / Num. of mol.: 4 / Fragment: UNP residues 321-735 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Western equine encephalitis virus / Production host: Homo sapiens (human) / References: UniProt: Q1W679 #4: Sugar | ChemComp-NAG / Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Western equine encephalitis virus VLP in complex with a chimeric MXRA8 receptor (Avian D1 with Mammalian D2) Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 7.45 MDa / Experimental value: NO |
Source (natural) | Organism: Western equine encephalitis virus |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 46.45 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: cryoSPARC / Version: 4.01 / Category: 3D reconstruction | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.89 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 431316 / Symmetry type: POINT | ||||||||||||||||||||||||
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