Highly similar structural frames link the template tunnel and NTP entry tunnel to the exterior surface in RNA-dependent RNA polymerases

Lang, Dorothy M.; Zemla, A. T.; Zhou, C. L. Ecale

HmE forms part of the NTP entry tunnel and has a considerable amount of exposure on the surface of the protein. The species-specific loop within hmE is at the outermost edge of the protein, a feature found in other homomorphs (G, F2 and A; Figures 2A, 3A and 4A, respectively). Huang et al. (25) found that the Motif E loop region acts as a pivot point for thumb subdomain movement upon template-primer binding. Motif E may also function in the proper positioning of the thumb relative to the palm (5) . The turn of the loop projects into the active site cavity where it has been implicated in helping to position the C-terminal end of the primer strand for attachment to the a-phosphate of the NTP during phosphoryl transfer (56) . Motif E in HCV plays a role in binding the priming nucleotide (not the incoming nucleotides) (38) ; HCV has a longer loop ( Figure 9A ), possibly related to this function. In PV, the C-terminal of hmE (R402) emerges from the protein into the segment 28-SAFHYVFEG-36. This segment contains residues F30 and F34, which interact with W403 to maintain the polymerase structure (39) .