+
Open data
-
Basic information
Entry | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | 9H2 Fab-poliovirus 2 complex | ||||||||||||
![]() | Cryosparc sharpened | ||||||||||||
![]() |
| ||||||||||||
![]() | Complex / Fab / poliovirus / neutralizing / VIRUS-IMMUNE SYSTEM complex | ||||||||||||
Function / homology | ![]() symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / ribonucleoside triphosphate phosphatase activity / 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 / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / viral capsid / host cell ...symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / ribonucleoside triphosphate phosphatase activity / 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 / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / viral capsid / host cell / nucleoside-triphosphate phosphatase / channel activity / monoatomic ion transmembrane transport / symbiont-mediated suppression of host gene expression / host cell cytoplasm / RNA helicase activity / endocytosis involved in viral entry into host cell / symbiont-mediated activation of host autophagy / symbiont entry into host cell / RNA-directed RNA polymerase / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed 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 Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.73 Å | ||||||||||||
![]() | Charnesky AJ | ||||||||||||
Funding support | ![]()
| ||||||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 633.6 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 23.1 KB 23.1 KB | Display Display | ![]() |
Images | ![]() | 267.2 KB | ||
Filedesc metadata | ![]() | 6.6 KB | ||
Others | ![]() ![]() ![]() | 597.9 MB 621.8 MB 621.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 20.5 KB | Display | |
Data in CIF | ![]() | 24.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8e8sMC ![]() 8e8lC ![]() 8e8rC ![]() 8e8xC ![]() 8e8yC ![]() 8e8zC C: citing same article ( M: atomic model generated by this map |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Cryosparc sharpened | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Additional map: DeepEMhancer sharpened
File | emd_27948_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | DeepEMhancer sharpened | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half Map A
File | emd_27948_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half Map A | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half Map B
File | emd_27948_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half Map B | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Human poliovirus 2
Entire | Name: ![]() |
---|---|
Components |
|
-Supramolecule #1: Human poliovirus 2
Supramolecule | Name: Human poliovirus 2 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 / NCBI-ID: 12083 / Sci species name: Human poliovirus 2 / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: No / Virus empty: No |
---|---|
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 |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 30.663457 KDa |
Sequence | String: NNLPDTQSSG PAHSKETPAL TAVETGATNP LVPSDTVQTR HVIQKRTRSE STVESFFARG ACVAIIEVDN DAPTKRASKL FSVWKITYK DTVQLRRKLE FFTYSRFDME FTFVVTSNYT DANNGHALNQ VYQIMYIPPG APIPGKWNDY TWQTSSNPSV F YTYGAPPA ...String: NNLPDTQSSG PAHSKETPAL TAVETGATNP LVPSDTVQTR HVIQKRTRSE STVESFFARG ACVAIIEVDN DAPTKRASKL FSVWKITYK DTVQLRRKLE FFTYSRFDME FTFVVTSNYT DANNGHALNQ VYQIMYIPPG APIPGKWNDY TWQTSSNPSV F YTYGAPPA RISVPYVGIA NAYSHFYDGF AKVPLAGQAS TEGDSLYGAA SLNDFGSLAV RVVNDHNPTK LTSKIRVYMK PK HVRVWCP RPPRAVPYYG PGVDYKDGLA PLPGKGLTTY 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 |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 29.045814 KDa |
Sequence | String: SVRVMQLTLG NSTITTQEAA NSVVAYGRWP EYIKDSEANP VDQPTEPDVA ACRFYTLDTV TWRKESRGWW WKLPDALKDM GLFGQNMFY HYLGRAGYTV HVQCNASKFH QGALGVFAVP EMCLAGDSTT HMFTKYENAN PGEKGGEFKG SFTLDTNATN P ARNFCPVD ...String: SVRVMQLTLG NSTITTQEAA NSVVAYGRWP EYIKDSEANP VDQPTEPDVA ACRFYTLDTV TWRKESRGWW WKLPDALKDM GLFGQNMFY HYLGRAGYTV HVQCNASKFH QGALGVFAVP EMCLAGDSTT HMFTKYENAN PGEKGGEFKG SFTLDTNATN P ARNFCPVD YLFGSGVLAG 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 |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 26.115852 KDa |
Sequence | String: GLPVLNTPGS NQYLTADNYQ SPCAIPEFDV TPPIDIPGEV RNMMELAEID TMIPLNLTNQ RKNTMDMYRV ELNDAAHSDT PILCLSLSP ASDPRLAHTM LGEILNYYTH WAGSLKFTFL FCGSMMATGK LLVSYAPPGA EAPKSRKEAM LGTHVIWDIG L QSSCTMVV ...String: GLPVLNTPGS NQYLTADNYQ SPCAIPEFDV TPPIDIPGEV RNMMELAEID TMIPLNLTNQ RKNTMDMYRV ELNDAAHSDT 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 |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 7.346957 KDa |
Sequence | String: GAQVSSQKVG AHENSNRAYG GSTINYTTIN YYRDSASNAA SKQDFAQDPS KFTEPIKDVL IKTAPTLN 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 |
---|---|
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 |
---|---|
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 |
---|---|
Molecular weight | Theoretical: 256.424 Da |
Chemical component information | ![]() ChemComp-PLM: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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: ![]() |
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 |
---|---|
Final reconstruction | Applied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 2.73 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 11599 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: PROJECTION MATCHING |