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- EMDB-12342: 1918 H1N1 Viral influenza polymerase heterotrimer - full transcri... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-12342 | ||||||||||||
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Title | 1918 H1N1 Viral influenza polymerase heterotrimer - full transcriptase (Class1) | ||||||||||||
![]() | Original refinement map. Used as input for deepEMhancer map. | ||||||||||||
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Function / homology | ![]() IgG binding / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | ||||||||||||
Method | ![]() ![]() | ||||||||||||
![]() | 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 | ![]() | 32 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.7 KB 23.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.8 KB | Display | ![]() |
Images | ![]() | 71.1 KB | ||
Others | ![]() | 59.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7nhxMC ![]() 7nfqC ![]() 7nfrC ![]() 7nftC ![]() 7nhaC ![]() 7nhcC ![]() 7ni0C ![]() 7nikC ![]() 7nilC ![]() 7nirC ![]() 7nisC ![]() 7nj3C ![]() 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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Annotation | Original refinement map. Used as input for deepEMhancer map. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Map produced by deepEMhancer using the -p wideTarget.
File | emd_12342_additional_1.map | ||||||||||||
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Annotation | Map produced by deepEMhancer using the -p wideTarget. | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : 1918 Influenza virus polymerase heterotrimer in complex with vRNA...
Entire | Name: 1918 Influenza virus polymerase heterotrimer in complex with vRNA promoters |
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Components |
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-Supramolecule #1: 1918 Influenza virus polymerase heterotrimer in complex with vRNA...
Supramolecule | Name: 1918 Influenza virus polymerase heterotrimer in complex with vRNA promoters type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Influenza virus polymerase heterotrimer
Supramolecule | Name: Influenza virus polymerase heterotrimer / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() ![]() |
-Supramolecule #3: vRNA promoters
Supramolecule | Name: vRNA promoters / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4-#5 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: synthetic construct (others) |
-Macromolecule #1: Polymerase acidic protein
Macromolecule | Name: Polymerase acidic protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: ![]() |
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Source (natural) | Organism: ![]() ![]() Strain: A/Brevig Mission/1/1918 H1N1 |
Molecular weight | Theoretical: 82.707391 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MEDFVRQCFN PMIVELAEKA MKEYGEDLKI ETNKFAAICT HLEVCFMYSD FHFINERGES IIVESGDPNA LLKHRFEIIE GRDRTMAWT VVNSICNTTG AEKPKFLPDL YDYKENRFIE IGVTRREVHI YYLEKANKIK SEKTHIHIFS FTGEEMATKA D YTLDEESR ...String: MEDFVRQCFN PMIVELAEKA MKEYGEDLKI ETNKFAAICT HLEVCFMYSD FHFINERGES IIVESGDPNA LLKHRFEIIE GRDRTMAWT VVNSICNTTG AEKPKFLPDL YDYKENRFIE IGVTRREVHI YYLEKANKIK SEKTHIHIFS FTGEEMATKA D YTLDEESR ARIKTRLFTI RQEMASRGLW DSFRQSERGE ETIEERFEIT GTMRRLADQS LPPNFSSLEN FRAYVDGFEP NG YIEGKLS QMSKEVNARI EPFLKTTPRP LRLPDGPPCS QRSKFLLMDA LKLSIEDPSH EGEGIPLYDA IKCMRTFFGW KEP NVVKPH EKGINPNYLL AWKQVLAELQ DIENEEKIPK TKNMKKTSQL KWALGENMAP EKVDFDDCKD VSDLKQYDSD EPEL RSLAS WIQSEFNKAC ELTDSSWIEL DEIGEDVAPI EHIASMRRNY FTAEVSHCRA TEYIMKGVYI NTALLNASCA AMDDF QLIP MISKCRTKEG RRKTNLYGFI IKGRSHLRND TDVVNFVSME FSLTDPRLEP HKWEKYCVLE IGDMLLRSAI GQVSRP MFL YVRTNGTSKI KMKWGMEMRR CLLQSLQQIE SMIEAESSVK EKDMTKEFFE NKSETWPIGE SPKGVEEGSI GKVCRTL LA KSVFNSLYAS PQLEGFSAES RKLLLIVQAL RDNLEPGTFD LGGLYEAIEE CLINDPWVLL NASWFNSFLT HALR |
-Macromolecule #2: RNA-directed RNA polymerase catalytic subunit
Macromolecule | Name: RNA-directed RNA polymerase catalytic subunit / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: ![]() |
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Source (natural) | Organism: ![]() ![]() Strain: A/Brevig Mission/1/1918 H1N1 |
Molecular weight | Theoretical: 86.625211 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MDVNPTLLFL KVPAQNAIST TFPYTGDPPY SHGTGTGYTM DTVNRTHQYS EKGRWTTNTE TGAPQLNPID GPLPEDNEPS GYAQTDCVL EAMAFLEESH PGIFENSCLE TMEVVQQTRV DKLTQGRQTY DWTLNRNQPA ATALANTIEV FRSNGLTANE S GRLIDFLK ...String: MDVNPTLLFL KVPAQNAIST TFPYTGDPPY SHGTGTGYTM DTVNRTHQYS EKGRWTTNTE TGAPQLNPID GPLPEDNEPS GYAQTDCVL EAMAFLEESH PGIFENSCLE TMEVVQQTRV DKLTQGRQTY DWTLNRNQPA ATALANTIEV FRSNGLTANE S GRLIDFLK DVMESMDKEE MEITTHFQRK RRVRDNMTKK MVTQRTIGKK KQRLNKRSYL IRALTLNTMT KDAERGKLKR RA IATPGMQ IRGFVYFVET LARSICEKLE QSGLPVGGNE KKAKLANVVR KMMTNSQDTE LSFTITGDNT KWNENQNPRM FLA MITYIT RNQPEWFRNV LSIAPIMFSN KMARLGKGYM FESKSMKLRT QIPAEMLASI DLKYFNDSTR KKIEKIRPLL IDGT ASLSP GMMMGMFNML STVLGVSILN LGQKRYTKTT YWWDGLQSSD DFALIVNAPN HEGIQAGVDR FYRTCKLLGI NMSKK KSYI NRTGTFEFTS FFYRYGFVAN FSMELPSFGV SGINESADMS IGVTVIKNNM INNDLGPATA QMALQLFIKD YRYTYR CHR GDTQIQTRRS FEIKKLWEQT RSKAGLLVSD GGPNLYNIRN LHIPEVCLKW ELMDEDYQGR LCNPLNPFVS HKEIESV NN AVMMPAHGPA KNMEYDAVAT THSWIPKRNR SILNTSQRGI LEDEQMYQKC CNLFEKFFPS SSYRRPVGIS SMVEAMVS R ARIDARIDFE SGRIKKEEFA EIMKICSTIE ELRRQK |
-Macromolecule #3: Polymerase basic protein 2,Immunoglobulin G-binding protein A
Macromolecule | Name: Polymerase basic protein 2,Immunoglobulin G-binding protein A type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 102.377219 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MERIKELRDL MSQSRTREIL TKTTVDHMAI IKKYTSGRQE KNPALRMKWM MAMKYPITAD KRIMEMIPER NEQGQTLWSK TNDAGSDRV MVSPLAVTWW NRNGPTTSAV HYPKIYKTYF EKVERLKHGT FGPVHFRNQV KIRRRVDINP GHADLSAKEA Q DVIMEVVF ...String: MERIKELRDL MSQSRTREIL TKTTVDHMAI IKKYTSGRQE KNPALRMKWM MAMKYPITAD KRIMEMIPER NEQGQTLWSK TNDAGSDRV MVSPLAVTWW NRNGPTTSAV HYPKIYKTYF EKVERLKHGT FGPVHFRNQV KIRRRVDINP GHADLSAKEA Q DVIMEVVF PNEVGARILT SESQLTITKE KKEELQDCKI SPLMVAYMLE RELVRKTRFL PVAGGTSSVY IEVLHLTQGT CW EQMYTPG GEVRNDDVDQ SLIIAARNIV RRATVSADPL ASLLEMCHST QIGGIRMVDI LRQNPTEEQA VDICKAAMGL RIS SSFSFG GFTFKRTSGS SVKREEEVLT GNLQTLKIRV HEGYEEFTMV GRRATAILRK ATRRLIQLIV SGRDEQSIAE AIIV AMVFS QEDCMIKAVR GDLNFVNRAN QRLNPMHQLL RHFQKDAKVL FQNWGIEPID NVMGMIGILP DMTPSTEMSM RGVRV SKMG VDEYSSTERV VVSIDRFLRV RDQRGNVLLS PEEVSETQGT EKLTITYSSS MMWEVNGPES VLVNTYQWII RNWETV KIQ WSQNPTMLYN KMEFEPFQSL VPKAARGQYS GFVRTLFQQM RDVLGTFDTV QIIKLLPFAA APPKQSRMQF SSLTVNV RG SGMRILVRGN SPVFNYNKAT KRLTVLGKDA GALTEDPDEG TAGVESAVLR GFLILGKEDR RYGPALSINE LSNLAKGE K ANVLIGQGDV VLVMKRKRDS SILTDSQTAT KRIRMAINEN LYFQGELKTA ALAQHDEAVD NKFNKEQQNA FYEILHLPN LNEEQRNAFI QSLKDDPSQS ANLLAEAKKL NDAQAPKVDN KFNKEQQNAF YEILHLPNLN EEQRNAFIQS LKADPSQSAN LLAEAKKLN GAQAPKVDAN SAGKST |
-Macromolecule #4: RNA (5'-R(P*GP*GP*CP*CP*UP*GP*CP*U)-3')
Macromolecule | Name: RNA (5'-R(P*GP*GP*CP*CP*UP*GP*CP*U)-3') / type: rna / ID: 4 / Number of copies: 1 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 5.335125 KDa |
Sequence | String: GGCCUGCUUU UGCUAUU |
-Macromolecule #5: RNA (5'-R(P*AP*GP*UP*AP*GP*AP*AP*AP*CP*AP*AP*GP*GP*CP*C)-3')
Macromolecule | Name: RNA (5'-R(P*AP*GP*UP*AP*GP*AP*AP*AP*CP*AP*AP*GP*GP*CP*C)-3') type: rna / ID: 5 / Number of copies: 1 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 4.862017 KDa |
Sequence | String: AGUAGAAACA AGGCC |
-Experimental details
-Structure determination
Method | ![]() |
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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 / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV / Details: 3.5 second blot and 3 microlitres sample.. |
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Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Number grids imaged: 1 / Number real images: 9413 / Average exposure time: 5.0 sec. / Average electron dose: 61.5 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |