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Yorodumi- EMDB-9394: Electron Cryo-Microscopy Of Chikungunya VLP in complex with mouse... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9394 | |||||||||
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Title | Electron Cryo-Microscopy Of Chikungunya VLP in complex with mouse Mxra8 receptor | |||||||||
Map data | Chikungunya VLP 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 / symbiont-mediated suppression of host toll-like receptor signaling pathway / host cell cytoplasm / 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 / symbiont-mediated suppression of host toll-like receptor signaling pathway / host cell cytoplasm / cell differentiation / cell adhesion / symbiont entry into host cell / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / host cell nucleus / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / cell surface / proteolysis / RNA binding / membrane / nucleus / cytoplasm Similarity search - Function | |||||||||
Biological species | Chikungunya virus (strain 37997) / Mus musculus (house mouse) / Chikungunya virus strain Senegal 37997 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.06 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_9394.map.gz | 765.6 MB | EMDB map data format | |
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Header (meta data) | emd-9394-v30.xml emd-9394.xml | 21.6 KB 21.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_9394_fsc.xml | 20.6 KB | Display | FSC data file |
Images | emd_9394.png | 191.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9394 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9394 | HTTPS FTP |
-Validation report
Summary document | emd_9394_validation.pdf.gz | 189 KB | Display | EMDB validaton report |
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Full document | emd_9394_full_validation.pdf.gz | 188.6 KB | Display | |
Data in XML | emd_9394_validation.xml.gz | 501 B | Display | |
Data in CIF | emd_9394_validation.cif.gz | 372 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9394 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9394 | HTTPS FTP |
-Related structure data
Related structure data | 6nk6MC 9393C 9395C 6nk3C 6nk5C 6nk7C 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_9394.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Chikungunya VLP 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 like particle with Mxra8
Entire | Name: Chikungunya virus like particle with Mxra8 |
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Components |
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-Supramolecule #1: Chikungunya virus like particle with Mxra8
Supramolecule | Name: Chikungunya virus like particle with Mxra8 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 Details: VLP Produced by PaxVax Corporation, Redwood CA, USA. Mouse Mxra8 produced in HEK293 cells. |
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-Supramolecule #2: Chikungunya virus like particle
Supramolecule | Name: Chikungunya virus like particle / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2-#4 |
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Source (natural) | Organism: Chikungunya virus (strain 37997) / Strain: 37997 |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant strain: HEK293F |
-Supramolecule #3: Mxra8 receptor
Supramolecule | Name: Mxra8 receptor / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant strain: HEK293F |
-Macromolecule #1: Matrix remodeling-associated protein 8
Macromolecule | Name: Matrix remodeling-associated protein 8 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 30.819457 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 QVTEPAFEPP SA |
-Macromolecule #2: E1 glycoprotein
Macromolecule | Name: E1 glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Chikungunya virus strain Senegal 37997 / Strain: 37997 |
Molecular weight | Theoretical: 47.346715 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: YEHVTVIPNT VGVPYKTLVN RPGYSPMVLE MELQSVTLEP TLSLDYITCE YKTVIPSPYV KCCGTAECKD KSLPDYSCKV FTGVYPFMW GGAYCFCDAE NTQLSEAHVE KSESCKTEFA SAYRAHTASA SAKLRVLYQG NNITVAAYAN GDHAVTVKDA K FVVGPMSS ...String: YEHVTVIPNT VGVPYKTLVN RPGYSPMVLE MELQSVTLEP TLSLDYITCE YKTVIPSPYV KCCGTAECKD KSLPDYSCKV FTGVYPFMW GGAYCFCDAE NTQLSEAHVE KSESCKTEFA SAYRAHTASA SAKLRVLYQG NNITVAAYAN GDHAVTVKDA K FVVGPMSS AWTPFDNKIV VYKGDVYNMD YPPFGAGRPG QFGDIQSRTP ESKDVYANTQ LVLQRPAAGT VHVPYSQAPS GF KYWLKER GASLQHTAPF GCQIATNPVR AVNCAVGNIP ISIDIPDAAF TRVVDAPSVT DMSCEVPACT HSSDFGGVAI IKY TASKKG KCAVHSMTNA VTIREADVEV EGNSQLQISF STALASAEFR VQVCSTQVHC AAACHPPKDH IVNYPASHTT LGVQ DISTT AMSWVQKITG GVGLIVAVAA LILIVVLCVS FSRH |
-Macromolecule #3: E2 glycoprotein
Macromolecule | Name: E2 glycoprotein / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Chikungunya virus strain Senegal 37997 / Strain: 37997 |
Molecular weight | Theoretical: 46.858312 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: NFNVYKATRP YLAHCPDCGE GHSCHSPIAL ERIRNEATDG TLKIQVSLQI GIKTDDSHDW TKLRYMDSHT PADAERAGLL VRTSAPCTI TGTMGHFILA RCPKGETLTV GFTDSRKISH TCTHPFHHEP PVIGRERFHS RPQHGKELPC STYVQSTAAT A EEIEVHMP ...String: NFNVYKATRP YLAHCPDCGE GHSCHSPIAL ERIRNEATDG TLKIQVSLQI GIKTDDSHDW TKLRYMDSHT PADAERAGLL VRTSAPCTI TGTMGHFILA RCPKGETLTV GFTDSRKISH TCTHPFHHEP PVIGRERFHS RPQHGKELPC STYVQSTAAT A EEIEVHMP PDTPDRTLMT QQSGNVKITV NGQTVRYKCN CGGSNEGLTT TDKVINNCKI DQCHAAVTNH KNWQYNSPLV PR NAELGDR KGKIHIPFPL ANVTCRVPKA RNPTVTYGKN QVTMLLYPDH PTLLSYRNMG QEPNYHEEWV THKKEVTLTV PTE GLEVTW GNNEPYKYWP QMSTNGTAHG HPHEIILYYY ELYPTMTVVI VSVASFVLLS MVGTAVGMCV CARRRCITPY ELTP GATVP FLLSLLCCVR TTKA |
-Macromolecule #4: Capsid protein
Macromolecule | Name: Capsid protein / type: protein_or_peptide / ID: 4 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Chikungunya virus strain Senegal 37997 / Strain: 37997 |
Molecular weight | Theoretical: 16.458701 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: NDCIFEVKHE GKVMGYACLV GDKVMKPAHV KGTIDNADLA KLAFKRSSKY DLECAQIPVH MKSDASKFTH EKPEGYYNWH HGAVQYSGG RFTIPTGAGK PGDSGRPIFD NKGRVVAIVL GGANEGARTA LSVVTWNKDI VTKITPEGAE EW |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 12 / 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
Concentration | 0.33 mg/mL | |||||||||||||||||||||
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Buffer | pH: 7.4 Component:
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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: 277.15 K / Instrument: FEI VITROBOT MARK IV | |||||||||||||||||||||
Details | 0.33 mg/mL VLP + 15 mg/mL Mxra8 |
-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-6nk6: |