Fig. 7: LACV-L replication and transcription cycle models.

a Structure-based model of the mechanisms underlying LACV-L replication and transcription. All structures are displayed as surfaces with specific domains and features colored as in Figs. 1 and 2. The vRNA is shown as a line with the 5′/3′ ends colored in pink/yellow. At initiation, the 3′-vRNA terminus is released from the secondary binding site and brought into the RdRp active site where it is stabilized by the PR loop, that extends due to the endonuclease (ENDO) movement. If the flexible cap-binding domain (CBD) snatches a 5′-cap, important conformational changes of the CBD, the ENDO, the mid and the zinc-binding domain (ZBD) occur, triggering capped primer translocation into the ENDO active site (in red). Once cleaved (yellow star), an ENDO movement triggers the capped primer repositioning towards the RdRp active site. Early elongation induces extrusion of the template exit plug resulting in the template exit opening (yellow dotted circle). In late-elongation, the 3′-vRNA template end goes back to the secondary binding site. b, c Structure-based model of initiation by prime-and-realign for replication (b) and transcription (c). The 5′/3′-vRNA ends are respectively colored in pink and gold. The 5′-hook structure is represented as a dotted line. Incorporated nucleotides are colored in blue. The prime-and-realign loop (PR loop) is shown in pink. The binding pocket of nucleotides A6, C7, and A8 at priming stage is surrounded by a dotted square. The proposed successive steps of the models are presented from left to right. The main role of each step is indicated below each schematic.