Figure 4. Model for RNA Synthesis by the VSV L-P Complex.

(A) Model of an initiation complex. The priming loop of VSV L Cap is in green; the RdRp hairpin harboring polymerase active-site residues GDN is in cyan. Template and transcript nucleotides are from the crystal structure of the reovirus λ3 polymerase initiation complex (ReoV) (PDB: 1N1H) (Tao et al., 2002) superposed on the VSV L-P structure. The first phosphodiester bond of the transcript is formed between the nucleotide in the priming position and the incoming nucleotide. _LTrp1167 supports the priming nucleotide by a stacking interaction with the base.

(B) Model of an elongation complex. To allow the passage of the growing template-transcript RNA duplex, shown here from the superposed structure of transcribing rotavirus VP1 polymerase (RotaV) (PDB: 6OJ6) (Jenni et al., 2019), the priming loop may retract to a position similar to that seen in the structure of the HMPV polymerase (PDB: 6U5O).

(C) Tunnels in VSV L-P. Structure is cut open to expose central cavities. RNA template and transcript strands are from the rotavirus structure as in (B). The template-entry channel is at the bottom. The template-exit channel is at the rear, bottom left. Nucleotide substrates enter the catalytic site laterally from the right (shown by an arrow). Catalytic sites with conserved residues for polymerization (RdRp), capping (Cap), and methylation (MT) are show by colored spheres. The tunnel was probed after omitting priming loop residues 1152–1173. Priming loop retraction into the space between the Cap domain and the CD (asterisk) opens a continuous path for the transcript RNA (dashed line).

See also Table S2.