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- PDB-7nik: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8189 core -
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Open data
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Basic information
Entry | Database: PDB / ID: 7nik | ||||||||||||
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Title | 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8189 core | ||||||||||||
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![]() | VIRAL PROTEIN / Influenza / RNA polymerase / H1N1 / 1918 / nanobody | ||||||||||||
Function / homology | ![]() IgG binding / cap snatching / viral transcription / symbiont-mediated suppression of host mRNA transcription via inhibition of RNA polymerase II activity / host cell mitochondrion / 7-methylguanosine mRNA capping / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / virion component / endonuclease activity / host cell cytoplasm ...IgG binding / cap snatching / viral transcription / symbiont-mediated suppression of host mRNA transcription via inhibition of RNA polymerase II activity / host cell mitochondrion / 7-methylguanosine mRNA capping / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / virion component / endonuclease activity / host cell cytoplasm / Hydrolases; Acting on ester bonds / RNA-directed RNA polymerase / viral RNA genome replication / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / nucleotide binding / DNA-templated transcription / host cell nucleus / RNA binding / extracellular region / metal ion binding Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.2 Å | ||||||||||||
![]() | Keown, J.R. / Carrique, L. / Fodor, E. / Grimes, J.M. | ||||||||||||
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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 554 KB | Display | ![]() |
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PDB format | ![]() | 456.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 12361MC ![]() 7nfqC ![]() 7nfrC ![]() 7nftC ![]() 7nhaC ![]() 7nhcC ![]() 7nhxC ![]() 7ni0C ![]() 7nilC ![]() 7nirC ![]() 7nisC ![]() 7nj3C ![]() 7nj4C ![]() 7nj5C ![]() 7nj7C ![]() 7nk1C ![]() 7nk2C ![]() 7nk4C ![]() 7nk6C ![]() 7nk8C ![]() 7nkaC ![]() 7nkcC ![]() 7nkiC ![]() 7nkrC M: map data used to model this data 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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Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 82707.391 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Strain: A/Brevig Mission/1/1918 H1N1 / Gene: PA / Production host: ![]() ![]() References: UniProt: Q3HM39, Hydrolases; Acting on ester bonds |
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#2: Protein | Mass: 86625.211 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Strain: A/Brevig Mission/1/1918 H1N1 / Gene: PB1 / Production host: ![]() ![]() |
-RNA chain , 2 types, 2 molecules ED
#4: RNA chain | Mass: 5335.125 Da / Num. of mol.: 1 / Source method: obtained synthetically Source: (synth.) ![]() |
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#5: RNA chain | Mass: 4862.017 Da / Num. of mol.: 1 / Source method: obtained synthetically Source: (synth.) ![]() |
-Antibody , 2 types, 2 molecules CF
#3: Antibody | Mass: 102377.219 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Strain: A/Brevig Mission/1/1918 H1N1 / Gene: PB2, spa / Production host: ![]() ![]() |
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#6: Antibody | Mass: 14069.456 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||||
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/1 | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 64 e/Å2 / Detector mode: INTEGRATING / Film or detector model: FEI FALCON III (4k x 4k) |
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Processing
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 372000 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 6.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 53970 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 7HNA | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 91.75 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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