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- PDB-6qpg: Influenza A virus Polymerase Heterotrimer A/nt/60/1968(H3N2) in c... -
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Basic information
Entry | Database: PDB / ID: 6qpg | ||||||||||||
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Title | Influenza A virus Polymerase Heterotrimer A/nt/60/1968(H3N2) in complex with Nanobody NB8205 | ||||||||||||
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![]() | RNA BINDING PROTEIN / Influenza A / RNA polymerase / Influenza polymerase / Influenza dimer / RDRP / Nanobody / antiviral inhibitor | ||||||||||||
Function / homology | ![]() 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 ...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 / nucleotide binding / virus-mediated perturbation of host defense response / DNA-templated transcription / host cell nucleus / RNA binding / metal ion binding Similarity search - Function | ||||||||||||
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![]() | Fan, H.T. / Keown, J.R. / Fodor, E. / Grimes, J.M. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of influenza A virus RNA polymerase offer insight into viral genome replication. Authors: Haitian Fan / Alexander P Walker / Loïc Carrique / Jeremy R Keown / Itziar Serna Martin / Dimple Karia / Jane Sharps / Narin Hengrung / Els Pardon / Jan Steyaert / Jonathan M Grimes / Ervin Fodor / ![]() ![]() ![]() Abstract: Influenza A viruses are responsible for seasonal epidemics, and pandemics can arise from the transmission of novel zoonotic influenza A viruses to humans. Influenza A viruses contain a segmented ...Influenza A viruses are responsible for seasonal epidemics, and pandemics can arise from the transmission of novel zoonotic influenza A viruses to humans. Influenza A viruses contain a segmented negative-sense RNA genome, which is transcribed and replicated by the viral-RNA-dependent RNA polymerase (FluPol) composed of PB1, PB2 and PA subunits. Although the high-resolution crystal structure of FluPol of bat influenza A virus has previously been reported, there are no complete structures available for human and avian FluPol. Furthermore, the molecular mechanisms of genomic viral RNA (vRNA) replication-which proceeds through a complementary RNA (cRNA) replicative intermediate, and requires oligomerization of the polymerase-remain largely unknown. Here, using crystallography and cryo-electron microscopy, we determine the structures of FluPol from human influenza A/NT/60/1968 (H3N2) and avian influenza A/duck/Fujian/01/2002 (H5N1) viruses at a resolution of 3.0-4.3 Å, in the presence or absence of a cRNA or vRNA template. In solution, FluPol forms dimers of heterotrimers through the C-terminal domain of the PA subunit, the thumb subdomain of PB1 and the N1 subdomain of PB2. The cryo-electron microscopy structure of monomeric FluPol bound to the cRNA template reveals a binding site for the 3' cRNA at the dimer interface. We use a combination of cell-based and in vitro assays to show that the interface of the FluPol dimer is required for vRNA synthesis during replication of the viral genome. We also show that a nanobody (a single-domain antibody) that interferes with FluPol dimerization inhibits the synthesis of vRNA and, consequently, inhibits virus replication in infected cells. Our study provides high-resolution structures of medically relevant FluPol, as well as insights into the replication mechanisms of the viral RNA genome. In addition, our work identifies sites in FluPol that could be targeted in the development of antiviral drugs. | ||||||||||||
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-Validation report
Summary document | ![]() | 625 KB | Display | ![]() |
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Full document | ![]() | 809 KB | Display | |
Data in XML | ![]() | 297.6 KB | Display | |
Data in CIF | ![]() | 392 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4660C ![]() 4661C ![]() 4663C ![]() 4664C ![]() 4666C ![]() 4986C ![]() 6qnwC ![]() 6qpfC ![]() 6qwlC ![]() 6qx3C ![]() 6qx8C ![]() 6qxeC ![]() 6rr7C ![]() 5d98S S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
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