Extended Data Fig. 10: Proposed models for transcription initiation and co-factor binding. | Nature Microbiology

Extended Data Fig. 10: Proposed models for transcription initiation and co-factor binding.

From: Structure of severe fever with thrombocytopenia syndrome virus L protein elucidates the mechanisms of viral transcription initiation

Extended Data Fig. 10

a, A proposed speculative model of SFTSV transcription initiation. SFTSV-L is schematically represented, with the cap-binding pocket (red hollow stars) in the CBD domain, the RdRp catalytic center (deep red dots) and the active center of the endoN domain (orange stars) as marked. (1) During the early event of the cap-snatching process, the lariat domain loses its interaction with the RdRp domain to allow the L protein to transform into a fully open state. Meanwhile, the endoN domain is pulled out from the central position of the SFTSV-L, and the arm domain shifts to induce the removal of the Arg-finger in the block motif from the cap-binding pocket of the CBD domain. (2) After the host mRNA is captured, the endoN domain employs an ~180° rotation along its long axis, thus causing its active center to face the nucleotide chain of host mRNA, and cleaves it by using two cations as cofactors chelated by the conserved H...PD...D/E...K motif. If the structures of LACV-L 1750 and SFTSV-L are aligned using their RdRp cores as the reference, the cap-binding pocket in the SFTSV-L CBD domain will have a distance of ~80 Å relative to the position of the LACV-L endoN domain active center (Supplementary Fig. 5). We reason the lack of C-terminal parts in the structure of LACV-L 1750 abolishes the extensive interdomain interactions to maintain the compact structure and allow its endoN domain to be in a fully open state. (3) Then, the CBD anchors the snatched cap structure with additional nucleotides and transfers the 3' end nucleotide chain to the RdRp catalytic cavity. (4) The transcription of virus mRNA is thus elongated with the guidance by vRNA as the template, and the products will be released from the product exit tunnel. In this stage, the endoN domain is likely to stay out of the center of the L protein, allowing the product exit tunnel to be in a fully open state. Meanwhile, the lariat motif will go back to its initial state. b, The structures of SFTSV-L and RSV-L-P complex5 are aligned by their RdRp core and shown in the same orientation. The colors for SFTSV-L domains are the same as those in Fig. 1. The RdRp and the PRNTase domains of RSV-L are shown in pale cyan and cyan, respectively. The P proteins bound to RSV-L is shown as cartoon diagram, and its structurally equivalent position in SFTSV-L is framed out.

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