+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27943 | ||||||||||||
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Title | 9H2 Fab-poliovirus 1 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 symbiont-mediated suppression of host translation initiation / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / ribonucleoside triphosphate phosphatase activity / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid ...symbiont-mediated suppression of host translation initiation / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / ribonucleoside triphosphate phosphatase activity / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / : / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / host cell cytoplasm / RNA helicase activity / induction by virus of host autophagy / RNA-directed RNA polymerase / symbiont-mediated suppression of host gene expression / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / DNA-templated transcription / host cell nucleus / virion attachment to host cell / structural molecule activity / proteolysis / RNA binding / ATP binding / membrane / metal ion binding / cytoplasm Similarity search - Function | ||||||||||||
Biological species | Human poliovirus 1 Mahoney / Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.13 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_27943.map.gz | 631.3 MB | EMDB map data format | |
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Header (meta data) | emd-27943-v30.xml emd-27943.xml | 22.9 KB 22.9 KB | Display Display | EMDB header |
Images | emd_27943.png | 249.7 KB | ||
Filedesc metadata | emd-27943.cif.gz | 6.5 KB | ||
Others | emd_27943_additional_1.map.gz emd_27943_half_map_1.map.gz emd_27943_half_map_2.map.gz | 603.8 MB 612.9 MB 612.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27943 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27943 | HTTPS FTP |
-Related structure data
Related structure data | 8e8lMC 8e8rC 8e8sC 8e8xC 8e8yC 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_27943.map.gz / Format: CCP4 / Size: 669.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Cryosparc sharpened | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 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_27943_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_27943_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_27943_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 1 Mahoney
Entire | Name: Human poliovirus 1 Mahoney |
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Components |
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-Supramolecule #1: Human poliovirus 1 Mahoney
Supramolecule | Name: Human poliovirus 1 Mahoney / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 12081 / Sci species name: Human poliovirus 1 Mahoney / 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 1 Mahoney / Strain: Mahoney |
Molecular weight | Theoretical: 31.38424 KDa |
Sequence | String: ATSRDALPNT EASGPTHSKE IPALTAVETG ATNPLVPSDT VQTRHVVQHR SRSESSIESF FARGACVTIM TVDNPASTTN KDKLFAVWK ITYKDTVQLR RKLEFFTYSR FDMELTFVVT ANFTETNNGH ALNQVYQIMY VPPGAPVPEK WDDYTWQTSS N PSIFYTYG ...String: ATSRDALPNT EASGPTHSKE IPALTAVETG ATNPLVPSDT VQTRHVVQHR SRSESSIESF FARGACVTIM TVDNPASTTN KDKLFAVWK ITYKDTVQLR RKLEFFTYSR FDMELTFVVT ANFTETNNGH ALNQVYQIMY VPPGAPVPEK WDDYTWQTSS N PSIFYTYG TAPARISVPY VGISNAYSHF YDGFSKVPLK DQSAALGDSL YGAASLNDFG ILAVRVVNDH NPTKVTSKIR VY LKPKHIR VWCPRPPRAV AYYGPGVDYK DGTLTPLSTK DLTTY 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 1 Mahoney / Strain: Mahoney |
Molecular weight | Theoretical: 29.360998 KDa |
Sequence | String: GYSDRVLQLT LGNSTITTQE AANSVVAYGR WPEYLRDSEA NPVDQPTEPD VAACRFYTLD TVSWTKESRG WWWKLPDALR DMGLFGQNM YYHYLGRSGY TVHVQCNASK FHQGALGVFA VPEMCLAGDS NTTTMHTSYQ NANPGEKGGT FTGTFTPDNN Q TSPARRFC ...String: GYSDRVLQLT LGNSTITTQE AANSVVAYGR WPEYLRDSEA NPVDQPTEPD VAACRFYTLD TVSWTKESRG WWWKLPDALR DMGLFGQNM YYHYLGRSGY TVHVQCNASK FHQGALGVFA VPEMCLAGDS NTTTMHTSYQ NANPGEKGGT FTGTFTPDNN Q TSPARRFC PVDYLLGNGT LLGNAFVFPH QIINLRTNNC ATLVLPYVNS LSIDSMVKHN NWGIAILPLA PLNFASESSP EI PITLTIA PMCCEFNGLR NITLPRLQ 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 1 Mahoney / Strain: Mahoney |
Molecular weight | Theoretical: 26.235115 KDa |
Sequence | String: GLPVMNTPGS NQYLTADNFQ SPCALPEFDV TPPIDIPGEV KNMMELAEID TMIPFDLSAT KKNTMEMYRV RLSDKPHTDD PILCLSLSP ASDPRLSHTM LGEILNYYTH WAGSLKFTFL FCGSMMATGK LLVSYAPPGA DPPKKRKEAM LGTHVIWDIG L QSSCTMVV ...String: GLPVMNTPGS NQYLTADNFQ SPCALPEFDV TPPIDIPGEV KNMMELAEID TMIPFDLSAT KKNTMEMYRV RLSDKPHTDD PILCLSLSP ASDPRLSHTM LGEILNYYTH WAGSLKFTFL FCGSMMATGK LLVSYAPPGA DPPKKRKEAM LGTHVIWDIG L QSSCTMVV PWISNTTYRQ TIDDSFTEGG YISVFYQTRI VVPLSTPREM DILGFVSACN DFSVRLLRDT THIEQKA 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 1 Mahoney / Strain: Mahoney |
Molecular weight | Theoretical: 7.39305 KDa |
Sequence | String: GAQVSSQKVG AHENSNRAYG GSTINYTTIN YYRDSASNAA SKQDFSQDPS 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: 14.052716 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: LVQSGAELKK PGASVKFSCQ ASGFTFTTYD IHWVRQAPGQ GLEWMGMISP SRDSTIYAQK FQGRVTMTSD TSTSTVYMEL TSLRSEDTA LYYCATASRP SAWVFRSLYT YYYMDVWGTG TTVTVSS |
-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: 11.738903 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QSALTQPASV SGSPGQSITI SCTGTITDIG YYNYVSWYQQ HPGKAPKLII FDVTNRPSGV SDRFSGSKSG NTASLTISGL QAEDEGDYY CFSHRSNNIR VFGGGTKLTV L |
-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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: PROJECTION MATCHING |
Final reconstruction | Applied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 3.13 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 79471 |