Fig. 4: Elongation state of the L protein.

a Schematic presentation of the primed reaction was carried out to obtain the ELONGATION structure with the L protein stalled in an early elongation state. Nucleotides that are not visible or not clearly assignable from the experimental map are shown in grey italics. b ELONGATION structure of the L protein presented as a ribbon diagram in two views as indicated. EN, pyramid, α-bundle, mid-link and 627-like domains are coloured. 3′ vRNA is shown in orange, 5′ RNA in pink and product RNA in black. A dashed circle (hot pink) indicates the putative product exit. c Close-up on the mid-link and 627-like domains with the respective structural features labelled and the side chains of amino acids shown to be selectively important for viral transcription by Lehmann et al. 2014²⁴ shown as pink sticks. d Close-up on the CBD-like domain with side chains of amino acids that have been tested in the LASV mini-replicon system shown as sticks (pink—selective role in viral transcription; light grey—no significant reduction of L protein activity upon mutation shown by Lehmann et al. 2014²⁴; green—no or weak effect on L protein function upon mutation; dark red—potential selective role in viral transcription; dark grey—general defect of L protein activity upon mutation). Corresponding mini-replicon data are presented in Supplementary Fig. 8. e Close-up of the polymerase active site with the template RNA (orange), the product RNA (dark grey), the non-hydrolysable UTP (UMPNPP, yellow) and catalytic manganese ions (teal, A and B) involving the palm (red), fingers (blue), fingertips (magenta) and thumb (green) domains of the L protein. Important side chains are shown as sticks and conserved RdRp active site motifs (A–G) are labelled. The map around the UMPNPP and the manganese ions is shown as a grey mesh. f Template-product duplex of the polymerase active site is shown as a ribbon diagram with the product in black, the 3′ template in orange, the non-hydrolysable UTP (UMPNPP) in yellow and the catalytic manganese ions as teal spheres. The map around the ions and the UMPNPP is shown as a grey mesh.