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Open data
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Basic information
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Title | 9H2 Fab-Sabin poliovirus 3 complex | ||||||||||||
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Function / homology | ![]() caveolin-mediated endocytosis of virus by host cell / : / 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 / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | ![]() ![]() | ||||||||||||
![]() | Charnesky AJ | ||||||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 632.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.3 KB 23.3 KB | Display Display | ![]() |
Images | ![]() | 273.1 KB | ||
Filedesc metadata | ![]() | 6.7 KB | ||
Others | ![]() ![]() ![]() | 598.4 MB 612.3 MB 612.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8e8rMC ![]() 8e8lC ![]() 8e8sC ![]() 8e8xC ![]() 8e8yC ![]() 8e8zC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Cryosparc sharpened | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.2 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_27947_additional_1.map | ||||||||||||
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Annotation | DeepEMhancer sharpened | ||||||||||||
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Density Histograms |
-Half map: Half Map B
File | emd_27947_half_map_1.map | ||||||||||||
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Annotation | Half Map B | ||||||||||||
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-Half map: Half Map A
File | emd_27947_half_map_2.map | ||||||||||||
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Annotation | Half Map A | ||||||||||||
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Sample components
-Entire : Human poliovirus 3 strain Sabin
Entire | Name: ![]() |
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Components |
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-Supramolecule #1: Human poliovirus 3 strain Sabin
Supramolecule | Name: Human poliovirus 3 strain Sabin / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 / NCBI-ID: 270338 / Sci species name: Human poliovirus 3 strain Sabin / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: No / Virus empty: No |
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Host (natural) | Organism: ![]() ![]() |
-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: ![]() |
Molecular weight | Theoretical: 31.358221 KDa |
Sequence | String: QDSLPDTKAS GPAHSKEVPA LTAVETGATN PLAPSDTVQT RHVVQRRSRS ESTIESFFAR GACVAIIEVD NEQPTTRAQK LFAMWRITY KDTVQLRRKL EFFTYSRFDM EFTFVVTANF TNANNGHALN QVYQIMYIPP GAPTPKSWDD YTWQTSSNPS I FYTYGAAP ...String: QDSLPDTKAS GPAHSKEVPA LTAVETGATN PLAPSDTVQT RHVVQRRSRS ESTIESFFAR GACVAIIEVD NEQPTTRAQK LFAMWRITY KDTVQLRRKL EFFTYSRFDM EFTFVVTANF TNANNGHALN QVYQIMYIPP GAPTPKSWDD YTWQTSSNPS I FYTYGAAP ARISVPYVGL ANAYSHFYDG FAKVPLKTDA NDQIGDSLYS AMTVDDFGVL AVRVVNDHNP TKVTSKVRIY MK PKHVRVW CPRPPRAVPY YGPGVDYRNN LDPLSEKGLT TY 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: ![]() |
Molecular weight | Theoretical: 29.412111 KDa |
Sequence | String: YSDRVLQLTL GNSTITTQEA ANSVVAYGRW PEFIRDDEAN PVDQPTEPDV ATCRFYTLDT VMWGKESKGW WWKLPDALRD MGLFGQNMY YHYLGRSGYT VHVQCNASKF HQGALGVFAI PEYCLAGDSD KQRYTSYANA NPGERGGKFY SQFNKDNAVT S PKREFCPV ...String: YSDRVLQLTL GNSTITTQEA ANSVVAYGRW PEFIRDDEAN PVDQPTEPDV ATCRFYTLDT VMWGKESKGW WWKLPDALRD MGLFGQNMY YHYLGRSGYT VHVQCNASKF HQGALGVFAI PEYCLAGDSD KQRYTSYANA NPGERGGKFY SQFNKDNAVT S PKREFCPV DYLLGCGVLL GNAFVYPHQI INLRTNNSAT IVLPYVNALA IDSMVKHNNW GIAILPLSPL DFAQDSSVEI PI TVTIAPM CSEFNGLRNV TAPKFQ 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: ![]() |
Molecular weight | Theoretical: 25.950723 KDa |
Sequence | String: GLPVLNTPGS NQYLTSDNHQ SPCAIPEFDV TPPIDIPGEV KNMMELAEID TMIPLNLEST KRNTMDMYRV TLSDSADLSQ PILCLSLSP AFDPRLSHTM LGEVLNYYTH WAGSLKFTFL FCGSMMATGK ILVAYAPPGA QPPTSRKEAM LGTHVIWDLG L QSSCTMVV ...String: GLPVLNTPGS NQYLTSDNHQ SPCAIPEFDV TPPIDIPGEV KNMMELAEID TMIPLNLEST KRNTMDMYRV TLSDSADLSQ PILCLSLSP AFDPRLSHTM LGEVLNYYTH WAGSLKFTFL FCGSMMATGK ILVAYAPPGA QPPTSRKEAM LGTHVIWDLG L QSSCTMVV PWISNVTYRQ TTQDSFTEGG YISMFYQTRI VVPLSTPKSM SMLGFVSACN DFSVRLLRDT THISQSA 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: ![]() |
Molecular weight | Theoretical: 7.320917 KDa |
Sequence | String: GAQVSSQKVG AHENSNRAYG GSTINYTTIN YYKDSASNAA SKQDYSQDPS KFTEPLKDVL IKTAPALN 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: ![]() ![]() |
Molecular weight | Theoretical: 14.052716 KDa |
Recombinant expression | Organism: ![]() ![]() |
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: ![]() ![]() |
Molecular weight | Theoretical: 11.738903 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QSALTQPASV SGSPGQSITI SCTGTITDIG YYNYVSWYQQ HPGKAPKLII FDVTNRPSGV SDRFSGSKSG NTASLTISGL QAEDEGDYY CFSHRSNNIR VFGGGTKLTV L |
-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 | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
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 |
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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![]() |