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- EMDB-12371: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8196 core -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-12371 | ||||||||||||
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Title | 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8196 core | ||||||||||||
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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 | single particle reconstruction / cryo EM / Resolution: 4.48 Å | ||||||||||||
![]() | Keown JR / Carrique L / Fodor E / Grimes JM | ||||||||||||
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
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 2.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.7 KB 21.7 KB | Display Display | ![]() |
Images | ![]() | 50.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7nj3MC ![]() 7nfqC ![]() 7nfrC ![]() 7nftC ![]() 7nhaC ![]() 7nhcC ![]() 7nhxC ![]() 7ni0C ![]() 7nikC ![]() 7nilC ![]() 7nirC ![]() 7nisC ![]() 7nj4C ![]() 7nj5C ![]() 7nj7C ![]() 7nk1C ![]() 7nk2C ![]() 7nk4C ![]() 7nk6C ![]() 7nk8C ![]() 7nkaC ![]() 7nkcC ![]() 7nkiC ![]() 7nkrC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : 1918 Influenza virus polymerase heterotirmer in complex with vRNA...
+Supramolecule #1: 1918 Influenza virus polymerase heterotirmer in complex with vRNA...
+Supramolecule #2: Polymerase acidic protein, RNA-directed RNA polymerase catalytic ...
+Supramolecule #3: RNA
+Supramolecule #4: Nanobody8196 core
+Macromolecule #1: Polymerase acidic protein
+Macromolecule #2: RNA-directed RNA polymerase catalytic subunit
+Macromolecule #3: Polymerase basic protein 2,Immunoglobulin G-binding protein A
+Macromolecule #6: Nanobody8196 core
+Macromolecule #4: RNA (5'-R(P*GP*GP*CP*CP*UP*GP*CP*U)-3')
+Macromolecule #5: RNA (5'-R(P*AP*GP*UP*AP*GP*AP*AP*AP*CP*AP*AP*GP*GP*CP*C)-3')
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.3 mg/mL | |||||||||||||||
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Buffer | pH: 7.5 Component:
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: INTEGRATING / Average electron dose: 69.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
CTF correction | Software - Name: cryoSPARC (ver. 2.15) |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.48 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 2.15) / Number images used: 93519 |
Initial angle assignment | Type: RANDOM ASSIGNMENT / Software - Name: cryoSPARC (ver. 2.15) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |