Figure 8.

Overall scheme of nucleotide entry in RdRp. The new findings of the present work (from step 2 to step 6) are boxed. Crystal structures are available for a number of (+)-ssRNA RdRp of supergroup I and for HCV NS5B (supergroup II) for steps 1 (product state/pre-translocation) and 7 (ternary complex). Crystal structures for step 4 (post-translocation) are available only for supergroup I RdRp, and for step 6 (preinsertion) only for two enteroviruses (supergroup I). The RdRp domains are represented as three gray spheres (dark, palm; middle gray, fingers; light gray, thumb) with the entry loop of the RdRp-specific fingertips in pale green. The dsRNA is represented with yellow bases for template and salmon bases for primer. The central panel depicts the general reduction of distance between the base of the incoming nucleotide and the +1 base from the first nucleotide capture (2 to 3) to preinsertion (5 to 6), where Watson-Crick base pairing is established. Note that the actual values in early stages differ in different simulations and only converge at orientation.