Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies.
Journal, issue, pages	Nat Commun, Vol. 13, Issue 1, Page 251, Year 2022
Publish date	Jan 11, 2022
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 /
PubMed 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.
External links	Nat Commun / PubMed:35017564 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.68 - 6.72 Å
Structure data	12322 7nha EMDB-12322, PDB-7nha: 1918 H1N1 Viral influenza polymerase heterotrimer - Endonuclease and priming loop ordered (Class2a) Method: EM (single particle) / Resolution: 2.91 Å 12323 7nhc EMDB-12323, PDB-7nhc: 1918 H1N1 Viral influenza polymerase heterotrimer - Endonuclease ordered (Class2b) Method: EM (single particle) / Resolution: 2.87 Å 12342 7nhx EMDB-12342, PDB-7nhx: 1918 H1N1 Viral influenza polymerase heterotrimer - full transcriptase (Class1) Method: EM (single particle) / Resolution: 3.23 Å 12348 7ni0 EMDB-12348, PDB-7ni0: 1918 H1N1 Viral influenza polymerase heterotrimer - Replicase (class 3) Method: EM (single particle) / Resolution: 3.32 Å 12361 7nik EMDB-12361, PDB-7nik: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8189 core Method: EM (single particle) / Resolution: 6.2 Å 12362 7nil EMDB-12362, PDB-7nil: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8190 core Method: EM (single particle) / Resolution: 5.01 Å 12363 7nir EMDB-12363, PDB-7nir: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8191 core Method: EM (single particle) / Resolution: 6.7 Å 12364 7nis EMDB-12364, PDB-7nis: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8192 core Method: EM (single particle) / Resolution: 5.96 Å 12371 7nj3 EMDB-12371, PDB-7nj3: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8196 core Method: EM (single particle) / Resolution: 4.48 Å 12372 7nj4 EMDB-12372, PDB-7nj4: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8198 core Method: EM (single particle) / Resolution: 5.84 Å 12373 7nj5 EMDB-12373, PDB-7nj5: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8199 core Method: EM (single particle) / Resolution: 4.63 Å 12375 7nj7 EMDB-12375, PDB-7nj7: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8200 core Method: EM (single particle) / Resolution: 4.82 Å 12428 7nk1 EMDB-12428, PDB-7nk1: 1918 Influenza virus polymerase heterotirmer in complex with vRNA promoters and Nb8201 Method: EM (single particle) / Resolution: 4.22 Å 12429 7nk2 EMDB-12429, PDB-7nk2: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8202 core Method: EM (single particle) / Resolution: 4.84 Å 12430 7nk4 EMDB-12430, PDB-7nk4: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8203 core Method: EM (single particle) / Resolution: 5.32 Å 12431 7nk6 EMDB-12431, PDB-7nk6: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8204 Method: EM (single particle) / Resolution: 6.72 Å 12433 7nk8 EMDB-12433, PDB-7nk8: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8205 core Method: EM (single particle) / Resolution: 5.34 Å 12435 7nka EMDB-12435, PDB-7nka: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8206 Method: EM (single particle) / Resolution: 4.07 Å 12437 7nkc EMDB-12437, PDB-7nkc: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8207 Method: EM (single particle) / Resolution: 4.46 Å 12440 7nki EMDB-12440, PDB-7nki: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8209 core Method: EM (single particle) / Resolution: 4.67 Å 12447 7nkr EMDB-12447, PDB-7nkr: 1918 H1N1 Viral influenza polymerase heterotrimer with Nb8210 Method: EM (single particle) / Resolution: 5.6 Å PDB-7nfq: Fujian capmidlink domain in complex with Nb8193 Method: X-RAY DIFFRACTION / Resolution: 1.68 Å PDB-7nfr: Fujian capmidlink domain in complex with Nb8194 Method: X-RAY DIFFRACTION / Resolution: 1.88 Å PDB-7nft: Fujian capbinding domain in complex with Nb8208 Method: X-RAY DIFFRACTION / Resolution: 3.14 Å
Chemicals	ChemComp-GOL: GLYCEROL ChemComp-PEG: DI(HYDROXYETHYL)ETHER ChemComp-HOH: WATER ChemComp-SO4: SULFATE ION
Source	influenza a virus (strain a/brevig mission/1/1918 h1n1) synthetic construct (others) staphylococcus aureus (bacteria) influenza a virus (a/brevig mission/1/1918(h1n1)) camelidae mixed library (mammal) Influenza A virus (A/Brevig Mission/1/1918(H1N1)) influenza a virus (a/duck/fujian/13/2002(h5n1)) homo sapiens (human)
Keywords	VIRAL PROTEIN / Influenza polymerase / cap-binding domain / nanobody / Influenza / RNA polymerase / H1N1 / 1918 / Influenza virus / polymerase / RdRp