+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27950 | ||||||||||||
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Title | 9H2 Fab-Sabin poliovirus 2 complex | ||||||||||||
Map data | Cryosparc sharpened | ||||||||||||
Sample |
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Keywords | Complex / Fab / poliovirus / neutralizing / VIRUS-IMMUNE SYSTEM complex | ||||||||||||
Function / homology | Function and homology information picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / ribonucleoside triphosphate phosphatase activity / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression ...picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / ribonucleoside triphosphate phosphatase activity / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression / nucleoside-triphosphate phosphatase / channel activity / viral capsid / monoatomic ion transmembrane transport / RNA helicase activity / symbiont-mediated suppression of host innate immune response / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / host cell nucleus / virion attachment to host cell / structural molecule activity / proteolysis / RNA binding / ATP binding / metal ion binding Similarity search - Function | ||||||||||||
Biological species | Human poliovirus 2 strain Sabin / Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.5 Å | ||||||||||||
Authors | Charnesky AJ | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Nat Commun / Year: 2023 Title: A human monoclonal antibody binds within the poliovirus receptor-binding site to neutralize all three serotypes. Authors: Andrew J Charnesky / Julia E Faust / Hyunwook Lee / Rama Devudu Puligedda / Daniel J Goetschius / Nadia M DiNunno / Vaskar Thapa / Carol M Bator / Sung Hyun Joseph Cho / Rahnuma Wahid / ...Authors: Andrew J Charnesky / Julia E Faust / Hyunwook Lee / Rama Devudu Puligedda / Daniel J Goetschius / Nadia M DiNunno / Vaskar Thapa / Carol M Bator / Sung Hyun Joseph Cho / Rahnuma Wahid / Kutub Mahmood / Scott Dessain / Konstantin M Chumakov / Amy Rosenfeld / Susan L Hafenstein / Abstract: Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 ...Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 which is able to neutralize the three serotypes of poliovirus. Using cryo-EM we solve the near-atomic structures of 9H2 fragments (Fab) bound to capsids of poliovirus serotypes 1, 2, and 3. The Fab-virus complexes show that Fab interacts with the same binding mode for each serotype and at the same angle of interaction relative to the capsid surface. For each of the Fab-virus complexes, we find that the binding site overlaps with the poliovirus receptor (PVR) binding site and maps across and into a depression in the capsid called the canyon. No conformational changes to the capsid are induced by Fab binding for any complex. Competition binding experiments between 9H2 and PVR reveal that 9H2 impedes receptor binding. Thus, 9H2 outcompetes the receptor to neutralize poliovirus. The ability to neutralize all three serotypes, coupled with the critical importance of the conserved receptor binding site make 9H2 an attractive antiviral candidate for future development. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27950.map.gz | 631.8 MB | EMDB map data format | |
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Header (meta data) | emd-27950-v30.xml emd-27950.xml | 23.4 KB 23.4 KB | Display Display | EMDB header |
Images | emd_27950.png | 263.2 KB | ||
Filedesc metadata | emd-27950.cif.gz | 6.6 KB | ||
Others | emd_27950_additional_1.map.gz emd_27950_half_map_1.map.gz emd_27950_half_map_2.map.gz | 610.3 MB 613.2 MB 613.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27950 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27950 | HTTPS FTP |
-Validation report
Summary document | emd_27950_validation.pdf.gz | 1 MB | Display | EMDB validaton report |
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Full document | emd_27950_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | emd_27950_validation.xml.gz | 20.3 KB | Display | |
Data in CIF | emd_27950_validation.cif.gz | 24.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27950 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27950 | HTTPS FTP |
-Related structure data
Related structure data | 8e8yMC 8e8lC 8e8rC 8e8sC 8e8xC 8e8zC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_27950.map.gz / Format: CCP4 / Size: 669.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Cryosparc sharpened | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: DeepEMhancer sharpened
File | emd_27950_additional_1.map | ||||||||||||
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Annotation | DeepEMhancer sharpened | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half Map A
File | emd_27950_half_map_1.map | ||||||||||||
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Annotation | Half Map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half Map B
File | emd_27950_half_map_2.map | ||||||||||||
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Annotation | Half Map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Human poliovirus 2 strain Sabin
Entire | Name: Human poliovirus 2 strain Sabin |
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Components |
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-Supramolecule #1: Human poliovirus 2 strain Sabin
Supramolecule | Name: Human poliovirus 2 strain Sabin / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 / NCBI-ID: 990147 / Sci species name: Human poliovirus 2 strain Sabin / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: No / Virus empty: No |
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Host (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Capsid protein VP1
Macromolecule | Name: Capsid protein VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human poliovirus 2 strain Sabin / Strain: Sabin |
Molecular weight | Theoretical: 30.841754 KDa |
Sequence | String: NSLPDTKPSG PAHSKEIPAL TAVETGATNP LVPSDTVQTR HVIQRRTRSE STVESFFARG ACVAIIEVDN DAPTKRASRL FSVWKITYK DTVQLRRKLE FFTYSRFDME FTFVVTSNYI DANNGHALNQ VYQIMYIPPG APIPGKWNDY TWQTSSNPSV F YTYGAPPA ...String: NSLPDTKPSG PAHSKEIPAL TAVETGATNP LVPSDTVQTR HVIQRRTRSE STVESFFARG ACVAIIEVDN DAPTKRASRL FSVWKITYK DTVQLRRKLE FFTYSRFDME FTFVVTSNYI DANNGHALNQ VYQIMYIPPG APIPGKWNDY TWQTSSNPSV F YTYGAPPA RISVPYVGIA NAYSHFYDGF AKVPLAGQAS TEGDSLYGAA SLNDFGSLAV RVVNDHNPTR LTSKIRVYMK PK HVRVWCP RPPRAVPYFG PGVDYKDGLT PLPEKGLTTY UniProtKB: Genome polyprotein |
-Macromolecule #2: Capsid protein VP2
Macromolecule | Name: Capsid protein VP2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human poliovirus 2 strain Sabin / Strain: Sabin |
Molecular weight | Theoretical: 29.115908 KDa |
Sequence | String: SVRVMQLTLG NSTITTQEAA NSVVAYGRWP EYIRDTEANP VDQPTEPDVA ACRFYTLDTV TWRKESRGWW WKLPDALKDM GLFGQNMFY HYLGRAGYTV HVQCNASKFH QGALGVFAVP EMCLAGDSTT HMFTKYENAN PGEKGGEFKG SFTLDTNATN P ARNFCPVD ...String: SVRVMQLTLG NSTITTQEAA NSVVAYGRWP EYIRDTEANP VDQPTEPDVA ACRFYTLDTV TWRKESRGWW WKLPDALKDM GLFGQNMFY HYLGRAGYTV HVQCNASKFH QGALGVFAVP EMCLAGDSTT HMFTKYENAN PGEKGGEFKG SFTLDTNATN P ARNFCPVD YLFGSGVLVG NAFVYPHQII NLRTNNCATL VLPYVNSLSI DSMTKHNNWG IAILPLAPLD FATESSTEIP IT LTIAPMC CEFNGLRNIT VPRTQ UniProtKB: Genome polyprotein |
-Macromolecule #3: Capsid protein VP3
Macromolecule | Name: Capsid protein VP3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human poliovirus 2 strain Sabin / Strain: Sabin |
Molecular weight | Theoretical: 26.09183 KDa |
Sequence | String: GLPVLNTPGS NQYLTADNYQ SPCAIPEFDV TPPIDIPGEV RNMMELAEID TMIPLNLTSQ RKNTMDMYRV ELSDTAHSDT PILCLSLSP ASDPRLAHTM LGEILNYYTH WAGSLKFTFL FCGSMMATGK LLVSYAPPGA EAPKSRKEAM LGTHVIWDIG L QSSCTMVV ...String: GLPVLNTPGS NQYLTADNYQ SPCAIPEFDV TPPIDIPGEV RNMMELAEID TMIPLNLTSQ RKNTMDMYRV ELSDTAHSDT PILCLSLSP ASDPRLAHTM LGEILNYYTH WAGSLKFTFL FCGSMMATGK LLVSYAPPGA EAPKSRKEAM LGTHVIWDIG L QSSCTMVV PWISNTTYRQ TINDSFTEGG YISMFYQTRV VVPLSTPRKM DILGFVSACN DFSVRLLRDT THISQEA UniProtKB: Genome polyprotein |
-Macromolecule #4: Capsid protein VP4
Macromolecule | Name: Capsid protein VP4 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human poliovirus 2 strain Sabin / Strain: Sabin |
Molecular weight | Theoretical: 7.37705 KDa |
Sequence | String: GAQVSSQKVG AHENSNRAYG GSTINYTTIN YYRDSASNAA SKQDFAQDPS KFTEPIKDVL IKTAPMLN UniProtKB: Genome polyprotein |
-Macromolecule #5: 9H2 Fab heavy chain
Macromolecule | Name: 9H2 Fab heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.939559 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: VQSGAELKKP GASVKFSCQA SGFTFTTYDI HWVRQAPGQG LEWMGMISPS RDSTIYAQKF QGRVTMTSDT STSTVYMELT SLRSEDTAL YYCATASRPS AWVFRSLYTY YYMDVWGTGT TVTVSS |
-Macromolecule #6: 9H2 Fab light chain
Macromolecule | Name: 9H2 Fab light chain / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.610774 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SALTQPASVS GSPGQSITIS CTGTITDIGY YNYVSWYQQH PGKAPKLIIF DVTNRPSGVS DRFSGSKSGN TASLTISGLQ AEDEGDYYC FSHRSNNIRV FGGGTKLTVL |
-Macromolecule #7: PALMITIC ACID
Macromolecule | Name: PALMITIC ACID / type: ligand / ID: 7 / Number of copies: 1 / Formula: PLM |
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Molecular weight | Theoretical: 256.424 Da |
Chemical component information | ChemComp-PLM: |
-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 III (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Applied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 111182 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: PROJECTION MATCHING |