7ORJ

La Crosse virus polymerase at transcription capped RNA cleavage stage

Summary for 7ORJ

• Entry DOI: 10.2210/pdb7orj/pdb
• EMDB information: 13039
• Descriptor: RNA-directed RNA polymerase L, RNA (5'-R(P*AP*CP*GP*AP*GP*UP*GP*UP*CP*GP*UP*AP*CP*CP*AP*AP*G)-3'), RNA (5'-R(P*CP*UP*UP*GP*GP*UP*AP*GP*UP*AP*CP*AP*CP*UP*AP*CP*U)-3'), ... (6 entities in total)
• Functional Keywords: rna-dependent rna polymerase, viral protein
• Biological source: Bunyavirus La Crosse; More
• Total number of polymer chains: 4
• Total formula weight: 283608.60

Authors

Arragain, B.,Durieux Trouilleton, Q.,Baudin, F.,Cusack, S.,Schoehn, G.,Malet, H. (deposition date: 2021-06-06, release date: 2022-02-16, Last modification date: 2024-07-17)

Primary citation

Arragain, B.,Durieux Trouilleton, Q.,Baudin, F.,Provaznik, J.,Azevedo, N.,Cusack, S.,Schoehn, G.,Malet, H.
Structural snapshots of La Crosse virus polymerase reveal the mechanisms underlying Peribunyaviridae replication and transcription.
Nat Commun, 13:902-902, 2022

PubMed Abstract: Segmented negative-strand RNA bunyaviruses encode a multi-functional polymerase that performs genome replication and transcription. Here, we establish conditions for in vitro activity of La Crosse virus polymerase and visualize its conformational dynamics by cryo-electron microscopy, unveiling the precise molecular mechanics underlying its essential activities. We find that replication initiation is coupled to distal duplex promoter formation, endonuclease movement, prime-and-realign loop extension and closure of the polymerase core that direct the template towards the active site. Transcription initiation depends on C-terminal region closure and endonuclease movements that prompt primer cleavage prior to primer entry in the active site. Product realignment after priming, observed in replication and transcription, is triggered by the prime-and-realign loop. Switch to elongation results in polymerase reorganization and core region opening to facilitate template-product duplex formation in the active site cavity. The uncovered detailed mechanics should be helpful for the future design of antivirals counteracting bunyaviral life threatening pathogens.

PubMed: 35173159
DOI: 10.1038/s41467-022-28428-z

Experimental method

ELECTRON MICROSCOPY (3.9 Å)