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Yorodumi- EMDB-30476: Cryo-EM structure of Chikungunya virus in complex with Fab fragme... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30476 | |||||||||
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Title | Cryo-EM structure of Chikungunya virus in complex with Fab fragments of mAb CHK-124 | |||||||||
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Sample |
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Keywords | CHIKV / Fab / complex / VIRUS / IMMUNE SYSTEM-VIRUS complex | |||||||||
Function / homology | Function and homology information togavirin / T=4 icosahedral viral capsid / symbiont-mediated suppression of host toll-like receptor signaling pathway / host cell cytoplasm / membrane => GO:0016020 / 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 ...togavirin / T=4 icosahedral viral capsid / symbiont-mediated suppression of host toll-like receptor signaling pathway / host cell cytoplasm / membrane => GO:0016020 / 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 / virion membrane / structural molecule activity / proteolysis / RNA binding / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Chikungunya virus / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.2 Å | |||||||||
Authors | Zhou QF / Fox JM / Earnest JT / Ng TS / Kim AS / Fibriansah G / Kostyuchenko VA / Shu B / Diamond MS / Lok SM | |||||||||
Funding support | Singapore, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2020 Title: Structural basis of Chikungunya virus inhibition by monoclonal antibodies. Authors: Qun Fei Zhou / Julie M Fox / James T Earnest / Thiam-Seng Ng / Arthur S Kim / Guntur Fibriansah / Victor A Kostyuchenko / Jian Shi / Bo Shu / Michael S Diamond / Shee-Mei Lok / Abstract: Chikungunya virus (CHIKV) is an emerging viral pathogen that causes both acute and chronic debilitating arthritis. Here, we describe the functional and structural basis as to how two anti-CHIKV ...Chikungunya virus (CHIKV) is an emerging viral pathogen that causes both acute and chronic debilitating arthritis. Here, we describe the functional and structural basis as to how two anti-CHIKV monoclonal antibodies, CHK-124 and CHK-263, potently inhibit CHIKV infection in vitro and in vivo. Our in vitro studies show that CHK-124 and CHK-263 block CHIKV at multiple stages of viral infection. CHK-124 aggregates virus particles and blocks attachment. Also, due to antibody-induced virus aggregation, fusion with endosomes and egress are inhibited. CHK-263 neutralizes CHIKV infection mainly by blocking virus attachment and fusion. To determine the structural basis of neutralization, we generated cryogenic electron microscopy reconstructions of Fab:CHIKV complexes at 4- to 5-Å resolution. CHK-124 binds to the E2 domain B and overlaps with the Mxra8 receptor-binding site. CHK-263 blocks fusion by binding an epitope that spans across E1 and E2 and locks the heterodimer together, likely preventing structural rearrangements required for fusion. These results provide structural insight as to how neutralizing antibody engagement of CHIKV inhibits different stages of the viral life cycle, which could inform vaccine and therapeutic design. | |||||||||
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_30476.map.gz | 207.9 MB | EMDB map data format | |
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Header (meta data) | emd-30476-v30.xml emd-30476.xml | 15.1 KB 15.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_30476_fsc.xml | 21.2 KB | Display | FSC data file |
Images | emd_30476.png | 296.4 KB | ||
Filedesc metadata | emd-30476.cif.gz | 5.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30476 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30476 | HTTPS FTP |
-Validation report
Summary document | emd_30476_validation.pdf.gz | 611.8 KB | Display | EMDB validaton report |
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Full document | emd_30476_full_validation.pdf.gz | 611.3 KB | Display | |
Data in XML | emd_30476_validation.xml.gz | 17.8 KB | Display | |
Data in CIF | emd_30476_validation.cif.gz | 25.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30476 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30476 | HTTPS FTP |
-Related structure data
Related structure data | 7cvyMC 7cvzC 7cw0C 7cw2C 7cw3C M: atomic model generated by this map C: citing same article (ref.) |
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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_30476.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.71 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 in complex with Fab fragments of mAb CHK-124
Entire | Name: Chikungunya virus in complex with Fab fragments of mAb CHK-124 |
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Components |
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-Supramolecule #1: Chikungunya virus in complex with Fab fragments of mAb CHK-124
Supramolecule | Name: Chikungunya virus in complex with Fab fragments of mAb CHK-124 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Chikungunya virus
Supramolecule | Name: Chikungunya virus / type: organelle_or_cellular_component / ID: 2 / Parent: 1 / Macromolecule list: #3-#5 |
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Source (natural) | Organism: Chikungunya virus / Strain: Ross |
-Supramolecule #3: Fab region of CHK-124
Supramolecule | Name: Fab region of CHK-124 / type: organelle_or_cellular_component / ID: 3 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: Fab heavy chain
Macromolecule | Name: Fab heavy chain / 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: 23.874674 KDa |
Sequence | String: QLQESGGGLV QPGGSMKLSC VASGFTFSNY WMNWVRQSPE KGLEWVAQIR LKSDSYATYY ADSVKGRFTV SRDDSKSNVY LQMNSLRAE DTGIYYCTDF YGFGDFFPYW GQGTLVTVSS AKTTAPSVYP LAPVCGGTTG SSVTLGCLVK GYFPEPVTLT W NSGSLSSG ...String: QLQESGGGLV QPGGSMKLSC VASGFTFSNY WMNWVRQSPE KGLEWVAQIR LKSDSYATYY ADSVKGRFTV SRDDSKSNVY LQMNSLRAE DTGIYYCTDF YGFGDFFPYW GQGTLVTVSS AKTTAPSVYP LAPVCGGTTG SSVTLGCLVK GYFPEPVTLT W NSGSLSSG VHTFPALLQS GLYTLSSSVT VTSNTWPSQT ITCNVAHPAS STKVDKKIES RR |
-Macromolecule #2: Fab light chain
Macromolecule | Name: Fab light chain / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.512852 KDa |
Sequence | String: DIVMTQSPKF MSTSIGDRVS VTCQASQNVG TNVAWYQQKP GQSPKPLIYS ASYRYSGVPG RFTGSGSGTD FTLTINNVQS EDLADYFCQ QYNSFPLTFG AGTKLELKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS ...String: DIVMTQSPKF MSTSIGDRVS VTCQASQNVG TNVAWYQQKP GQSPKPLIYS ASYRYSGVPG RFTGSGSGTD FTLTINNVQS EDLADYFCQ QYNSFPLTFG AGTKLELKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS KDSTYSMSST LTLTKDEYER HNSYTCEATH KTSTSPIVKS FNRNE |
-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 |
Molecular weight | Theoretical: 16.428607 KDa |
Sequence | String: NDCIFEVKHE GKVTGYACLV GDKVMKPAHV KGTIDNADLA KLAFKRSSKY DLECAQIPVH MKSDASKFTH EKPEGYYNWH HGAVQYSGG RFTIPTGAGK PGDSGRPIFD NKGRVVAIVL GGANEGARTA LSVVTWNKDI VTKITPEGAE EW UniProtKB: Structural polyprotein |
-Macromolecule #4: E1 glycoprotein
Macromolecule | Name: E1 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 |
Molecular weight | Theoretical: 47.507023 KDa |
Sequence | String: YEHVTVIPNT VGVPYKTLVN RPGYSPMVLE MELLSVTLEP TLSLDYITCE YKTVIPSPYV KCCGTAECKD KNLPDYSCKV FTGVYPFMW GGAYCFCDAE NTQLSEAHVE KSESCKTEFA SAYRAHTASA SAKLRVLYQG NNITVTAYAN GDHAVTVKDA K FIVGPMSS ...String: YEHVTVIPNT VGVPYKTLVN RPGYSPMVLE MELLSVTLEP TLSLDYITCE YKTVIPSPYV KCCGTAECKD KNLPDYSCKV FTGVYPFMW GGAYCFCDAE NTQLSEAHVE KSESCKTEFA SAYRAHTASA SAKLRVLYQG NNITVTAYAN GDHAVTVKDA K FIVGPMSS AWTPFDNKIV VYKGDVYNMD YPPFGAGRPG QFGDIQSRTP ESKDVYANTQ LVLQRPAAGT VHVPYSQAPS GF KYWLKER GASLQHTAPF GCQIATNPVR AMNCAVGNMP ISIDIPDAAF TRVVDAPSLT DMSCEVPACT HSSDFGGVAI IKY AVSKKG KCAVHSMTNA VTIREAEIEV EGNSQLQISF STALASAEFR VQVCSTQVHC AAECHPPKDH IVNYPASHTT LGVQ DISAT AMSWVQKITG GVGLVVAVAA LILIVVLCVS FSRH UniProtKB: Togavirin |
-Macromolecule #5: E2 glycoprotein
Macromolecule | Name: E2 glycoprotein / type: protein_or_peptide / ID: 5 / Number of copies: 4 / Enantiomer: LEVO / EC number: togavirin |
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Source (natural) | Organism: Chikungunya virus |
Molecular weight | Theoretical: 46.705406 KDa |
Sequence | String: NFNVYKATRP YLAHCPDCGE GHSCHSPVAL ERIRNEATDG TLKIQVSLQI GIGTDDSHDW TKLRYMDNHI PADAGRAGLF VRTSAPCTI TGTMGHFILA RCPKGETLTV GFTDSRKISH SCTHPFHHDP PVIGREKFHS RPQHGKELPC STYVQSNAAT A EEIEVHMP ...String: NFNVYKATRP YLAHCPDCGE GHSCHSPVAL ERIRNEATDG TLKIQVSLQI GIGTDDSHDW TKLRYMDNHI PADAGRAGLF VRTSAPCTI TGTMGHFILA RCPKGETLTV GFTDSRKISH SCTHPFHHDP PVIGREKFHS RPQHGKELPC STYVQSNAAT A EEIEVHMP PDTPDRTLLS QQSGNVKITV NGRTVRYKCN CGGSNEGLIT TDKVINNCKV DQCHAAVTNH KKWQYNSPLV PR NAELGDR KGKIRIPFPL ANVTCMVPKA RNPTVTYGKN QVIMLLYPDH PTLLSYRSMG EEPNYQEEWV THKKEVVLTV PTE GLEVTW GNNEPYKYWP QLSANGTAHG HPHEIILYYY ELYPTMTVVV VSVASFILLS MVGMAVGMCM CARRRCITPY ELTP GATVP FLLSLICCIR TAKA |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Average electron dose: 20.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |