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Open data
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Basic information
Entry | Database: PDB / ID: 7nfq | |||||||||
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Title | Fujian capmidlink domain in complex with Nb8193 | |||||||||
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![]() | VIRAL PROTEIN / Influenza polymerase / cap-binding domain / nanobody | |||||||||
Function / homology | ![]() cap snatching / symbiont-mediated suppression of host mRNA transcription via inhibition of RNA polymerase II activity / host cell mitochondrion / 7-methylguanosine mRNA capping / virion component / viral RNA genome replication / RNA-dependent RNA polymerase activity / DNA-templated transcription / host cell nucleus / RNA binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Keown, J.R. / Grimes, J.M. / Fodor, E. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies. Authors: Jeremy R Keown / Zihan Zhu / Loïc Carrique / Haitian Fan / Alexander P Walker / Itziar Serna Martin / Els Pardon / Jan Steyaert / Ervin Fodor / Jonathan M Grimes / ![]() ![]() ![]() Abstract: Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA- ...Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 566.2 KB | Display | ![]() |
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PDB format | ![]() | 387.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7nfrC ![]() 7nftC ![]() 7nhaC ![]() 7nhcC ![]() 7nhxC ![]() 7ni0C ![]() 7nikC ![]() 7nilC ![]() 7nirC ![]() 7nisC ![]() 7nj3C ![]() 7nj4C ![]() 7nj5C ![]() 7nj7C ![]() 7nk1C ![]() 7nk2C ![]() 7nk4C ![]() 7nk6C ![]() 7nk8C ![]() 7nkaC ![]() 7nkcC ![]() 7nkiC ![]() 7nkrC ![]() 6s5vS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 | ![]()
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2 | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 34249.168 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: PB2 / Production host: ![]() ![]() #2: Protein | Mass: 13983.466 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Chemical | ChemComp-GOL / #4: Chemical | ChemComp-PEG / | #5: Water | ChemComp-HOH / | Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.29 Å3/Da / Density % sol: 46.32 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: 20% w/v PEG3350 and 0.2 M (NH4)2 citrate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: May 14, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9762 Å / Relative weight: 1 |
Reflection | Resolution: 1.68→44.31 Å / Num. obs: 69149 / % possible obs: 70.31 % / Redundancy: 2 % / Biso Wilson estimate: 28.16 Å2 / CC1/2: 1 / Net I/σ(I): 23.17 |
Reflection shell | Resolution: 1.68→1.743 Å / Num. unique obs: 767 / CC1/2: 0.292 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 6S5V Resolution: 1.68→44.31 Å / SU ML: 0.1727 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 28.9662 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 35.39 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.68→44.31 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 4.58878721433 Å / Origin y: 10.3509992209 Å / Origin z: 18.7829446686 Å
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Refinement TLS group | Selection details: all |