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Yorodumi- EMDB-9395: Electron Cryo-Microscopy of Chikungunya in Complex with Mouse Mxr... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9395 | |||||||||
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Title | Electron Cryo-Microscopy of Chikungunya in Complex with Mouse Mxra8 Receptor | |||||||||
Map data | Chikungunya in Complex with Mouse Mxra8 Receptor | |||||||||
Sample |
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Function / homology | Function and homology information establishment of glial blood-brain barrier / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / Post-translational protein phosphorylation / togavirin / T=4 icosahedral viral capsid / ciliary membrane / bicellular tight junction / host cell cytoplasm / membrane => GO:0016020 / cell differentiation ...establishment of glial blood-brain barrier / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / Post-translational protein phosphorylation / togavirin / T=4 icosahedral viral capsid / ciliary membrane / bicellular tight junction / host cell cytoplasm / membrane => GO:0016020 / cell differentiation / cell adhesion / 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 / cell surface / proteolysis / nucleus / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Chikungunya virus / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.99 Å | |||||||||
Authors | Basore K / Kim AS / Nelson CA / Fremont DH / Center for Structural Genomics of Infectious Diseases (CSGID) | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Cell / Year: 2019 Title: Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor. Authors: Katherine Basore / Arthur S Kim / Christopher A Nelson / Rong Zhang / Brittany K Smith / Carla Uranga / Lo Vang / Ming Cheng / Michael L Gross / Jonathan Smith / Michael S Diamond / Daved H Fremont / Abstract: Mxra8 is a receptor for multiple arthritogenic alphaviruses that cause debilitating acute and chronic musculoskeletal disease in humans. Herein, we present a 2.2 Å resolution X-ray crystal ...Mxra8 is a receptor for multiple arthritogenic alphaviruses that cause debilitating acute and chronic musculoskeletal disease in humans. Herein, we present a 2.2 Å resolution X-ray crystal structure of Mxra8 and 4 to 5 Å resolution cryo-electron microscopy reconstructions of Mxra8 bound to chikungunya (CHIKV) virus-like particles and infectious virus. The Mxra8 ectodomain contains two strand-swapped Ig-like domains oriented in a unique disulfide-linked head-to-head arrangement. Mxra8 binds by wedging into a cleft created by two adjacent CHIKV E2-E1 heterodimers in one trimeric spike and engaging a neighboring spike. Two binding modes are observed with the fully mature VLP, with one Mxra8 binding with unique contacts. Only the high-affinity binding mode was observed in the complex with infectious CHIKV, as viral maturation and E3 occupancy appear to influence receptor binding-site usage. Our studies provide insight into how Mxra8 binds CHIKV and creates a path for developing alphavirus entry inhibitors. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9395.map.gz | 764.4 MB | EMDB map data format | |
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Header (meta data) | emd-9395-v30.xml emd-9395.xml | 22.9 KB 22.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_9395_fsc.xml | 20.7 KB | Display | FSC data file |
Images | emd_9395.png | 161 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9395 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9395 | HTTPS FTP |
-Validation report
Summary document | emd_9395_validation.pdf.gz | 188.8 KB | Display | EMDB validaton report |
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Full document | emd_9395_full_validation.pdf.gz | 188.3 KB | Display | |
Data in XML | emd_9395_validation.xml.gz | 501 B | Display | |
Data in CIF | emd_9395_validation.cif.gz | 371 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9395 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9395 | HTTPS FTP |
-Related structure data
Related structure data | 6nk7MC 9393C 9394C 6nk3C 6nk5C 6nk6C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9395.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Chikungunya in Complex with Mouse Mxra8 Receptor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.403 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Chikungunya virus with Mxra8 receptor
Entire | Name: Chikungunya virus with Mxra8 receptor |
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Components |
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-Supramolecule #1: Chikungunya virus with Mxra8 receptor
Supramolecule | Name: Chikungunya virus with Mxra8 receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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-Supramolecule #2: Chikungunya virus
Supramolecule | Name: Chikungunya virus / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Chikungunya virus / Strain: 181/25 |
Recombinant expression | Organism: Chlorocebus aethiops (grivet) / Recombinant cell: Vero |
-Supramolecule #3: mouse Mxra8 receptor ectodomain
Supramolecule | Name: mouse Mxra8 receptor ectodomain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #5 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293 |
-Macromolecule #1: E1 glycoprotein
Macromolecule | Name: E1 glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO / EC number: togavirin |
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Source (natural) | Organism: Chikungunya virus / Strain: 181/25 |
Molecular weight | Theoretical: 47.497906 KDa |
Recombinant expression | Organism: Chlorocebus aethiops (grivet) |
Sequence | String: YEHVTVIPNT VGVPYKTLVN RPGYSPMVLE MELLSVTLEP TLSLDYITCE YKTVIPSPYV KCCGTAECKD KSLPDYSCKV FTGVYPFMW GGAYCFCDTE NTQLSEAHVE KSESCKTEFA SAYRAHTASA SAKLRVLYQG NNVTVSAYAN GDHAVTVKDA K FIVGPMSS ...String: YEHVTVIPNT VGVPYKTLVN RPGYSPMVLE MELLSVTLEP TLSLDYITCE YKTVIPSPYV KCCGTAECKD KSLPDYSCKV FTGVYPFMW GGAYCFCDTE NTQLSEAHVE KSESCKTEFA SAYRAHTASA SAKLRVLYQG NNVTVSAYAN GDHAVTVKDA K FIVGPMSS AWTPFDNKIV VYKGDVYNMD YPPFGAGRPG QFGDIQSRTP ESEDVYANTQ LVLQRPSAGT VHVPYSQAPS GF KYWLKER GASLQHTAPF GCQIATNPVR AMNCAVGNMP ISIDIPDAAF TRVVDAPSLT DMSCEVPACT HSSDFGGVAI IKY AASKKG KCAVHSMTNA VTIREAEIEV EGNSQLQISF STALASAEFR VQVCSTQVHC AAECHPPKDH IVNYPASHTT LGVQ DISVT AMSWVQKITG GVGLVVAVAA LILIVVLCVS FSRH |
-Macromolecule #2: E2 glycoprotein
Macromolecule | Name: E2 glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO / EC number: togavirin |
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Source (natural) | Organism: Chikungunya virus / Strain: 181/25 |
Molecular weight | Theoretical: 47.077719 KDa |
Recombinant expression | Organism: Chlorocebus aethiops (grivet) |
Sequence | String: NFNVYKAIRP YLAHCPDCGE GHSCHSPVAL ERIRNEATDG TLKIQVSLQI GIKTDDSHDW TKLRYMDNHM PADAERARLF VRTSAPCTI TGTMGHFILA RCPKGETLTV GFTDGRKISH SCTHPFHHDP PVIGREKFHS RPQHGRELPC STYAQSTAAT A EEIEVHMP ...String: NFNVYKAIRP YLAHCPDCGE GHSCHSPVAL ERIRNEATDG TLKIQVSLQI GIKTDDSHDW TKLRYMDNHM PADAERARLF VRTSAPCTI TGTMGHFILA RCPKGETLTV GFTDGRKISH SCTHPFHHDP PVIGREKFHS RPQHGRELPC STYAQSTAAT A EEIEVHMP PDTPDRTLMS QQSGNVKITV NSQTVRYKCN CGDSNEGLTT TDKVINNCKV DQCHAAVTNH KKWQYNSPLV PR NAELGDR KGKVHIPFPL ANVTCRVPKA RNPTVTYGKN QVIMLLYPDH PTLLSYRNMG EEPNYQEEWV THKKEIRLTV PTE GLEVTW GNNEPYKYWP QLSTNGTAHG HPHEIILYYY ELYPTMTVVV VSVASFVLLS MVGVAVGMCM CARRRCITPY ELTP GATVP FLLSLICCIR TAKA |
-Macromolecule #3: Capsid protein
Macromolecule | Name: Capsid protein / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO / EC number: togavirin |
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Source (natural) | Organism: Chikungunya virus / Strain: 181/25 |
Molecular weight | Theoretical: 16.428607 KDa |
Recombinant expression | Organism: Chlorocebus aethiops (grivet) |
Sequence | String: NDCIFEVKHE GKVTGYACLV GDKVMKPAHV KGTIDNADLA KLAFKRSSKY DLECAQIPVH MKSDASKFTH EKPEGYYNWH HGAVQYSGG RFTIPTGAGK PGDSGRPIFD NKGRVVAIVL GGANEGARTA LSVVTWNKDI VTKITPEGAE EW |
-Macromolecule #4: E3 glycoprotein
Macromolecule | Name: E3 glycoprotein / type: protein_or_peptide / ID: 4 / Number of copies: 4 / Enantiomer: LEVO / EC number: togavirin |
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Source (natural) | Organism: Chikungunya virus / Strain: 181/25 |
Molecular weight | Theoretical: 6.95507 KDa |
Recombinant expression | Organism: Chlorocebus aethiops (grivet) |
Sequence | String: PVMCLLANTT FPCSQPPCTP CCYEKEPEET LRMLEDNVMR PGYYQLLQAS LTCSPHRQRR |
-Macromolecule #5: Matrix remodeling-associated protein 8
Macromolecule | Name: Matrix remodeling-associated protein 8 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 30.022596 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SSSLVSESVV SLAAGTQAVL RCQSPRMVWT QDRLHDRQRV VHWDLSGGPG SQRRRLVDMY SAGEQRVYEP RDRDRLLLSP SAFHDGNFS LLIRAVDRGD EGVYTCNLHH HYCHLDESLA VRLEVTEDPL LSRAYWDGEK EVLVVAHGAP ALMTCINRAH V WTDRHLEE ...String: SSSLVSESVV SLAAGTQAVL RCQSPRMVWT QDRLHDRQRV VHWDLSGGPG SQRRRLVDMY SAGEQRVYEP RDRDRLLLSP SAFHDGNFS LLIRAVDRGD EGVYTCNLHH HYCHLDESLA VRLEVTEDPL LSRAYWDGEK EVLVVAHGAP ALMTCINRAH V WTDRHLEE AQQVVHWDRQ LPGVSHDRAD RLLDLYASGE RRAYGPPFLR DRVSVNTNAF ARGDFSLRID ELERADEGIY SC HLHHHYC GLHERRVFHL QVTE |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 5 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.2 Component:
Details: Mxra8 at pH 7.4 | ||||||||||||||
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Grid | Model: Quantifoil R2/2 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Support film - Film thickness: 120.0 nm / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Atmosphere: OTHER / Details: 0.458 mbar.l/s O2 and 0.11 mbar.l/s H2 | ||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.00 K / Instrument: FEI VITROBOT MARK IV | ||||||||||||||
Details | Chikungunya virus grown in Vero cells + 15 mg/mL Mxra8 expressed in HEK293 cells |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average exposure time: 0.3 sec. / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: OTHER |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Space: REAL / Protocol: FLEXIBLE FIT | ||||||||||||||||
Output model | PDB-6nk7: |