6QCX

Crystal structure of influenza B polymerase initiation state with capped 15-mer RNA primer

Summary for 6QCX

• Entry DOI: 10.2210/pdb6qcx/pdb
• Related: 6QCV 6QCW
• Descriptor: Polymerase acidic protein, RNA-directed RNA polymerase catalytic subunit, Polymerase basic protein 2, ... (9 entities in total)
• Functional Keywords: rna dependent rna polymerase, viral protein
• Biological source: Influenza B virus (B/Memphis/13/2003); More
• Total number of polymer chains: 6
• Total formula weight: 279494.93

Authors

Cusack, S.,Drncova, P. (deposition date: 2018-12-31, release date: 2019-06-05, Last modification date: 2024-02-28)

Primary citation

Kouba, T.,Drncova, P.,Cusack, S.
Structural snapshots of actively transcribing influenza polymerase.
Nat.Struct.Mol.Biol., 26:460-470, 2019

PubMed Abstract: Influenza virus RNA-dependent RNA polymerase uses unique mechanisms to transcribe its single-stranded genomic viral RNA (vRNA) into messenger RNA. The polymerase is initially bound to a promoter comprising the partially base-paired 3' and 5' extremities of the RNA. A short, capped primer, 'cap-snatched' from a nascent host polymerase II transcript, is directed towards the polymerase active site to initiate RNA synthesis. Here we present structural snapshots, as determined by X-ray crystallography and cryo-electron microscopy, of actively initiating influenza polymerase as it transitions towards processive elongation. Unexpected conformational changes unblock the active site cavity to allow establishment of a nine-base-pair template-product RNA duplex before the strands separate into distinct exit channels. Concomitantly, as the template translocates, the promoter base pairs are broken and the template entry region is remodeled. These structures reveal details of the influenza polymerase active site that will help optimize nucleoside analogs or other compounds that directly inhibit viral RNA synthesis.

PubMed: 31160782
DOI: 10.1038/s41594-019-0232-z

Experimental method

X-RAY DIFFRACTION (3.08 Å)