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

Motif B is a component of the largest homomorph identified in the RdRps. The homomorph begins 21 residues upstream from Motif B and extends 10 residues downstream. The motif is 15 residues long. The size of the homomorph is consistent in most species. The structurally aligned sequences that comprise the homomorph are shown in the top section of Figure 5A . They include all the RdRps in the sample set plus TERT (RdDp). Each of In cells with a light blue background filled with a number, the number is the sequence position of the adjacent matches for each species; numbers in the white column between them summarize the length of sequence that the non-matched sequence represents in each species. In this segment there are more residues in each species than between the corresponding residues in PV, indicating that this region is a loop that is absent in PV, and the loop length varies by species. At the left of the alignment (209-214, uncolored), there is a structure common to several species, but too few to qualify the region as part of the homomorph. (B) In this figure of poliovirus (PDB:1RA6), the N-terminal segment of the homomorph is blue and the C-terminal segment is brown. The terminal residues of HmA are at the exterior surface of the protein (PDB:1RA6). Motif A is centered within the homomorph at the wall of the template tunnel. (C) The terminal residues of the homomorph and the helix adjacent to each are constituents of the protein surface. (D) In PV, an insertion (red) at the C-terminal edge of the motif is lethal: L241-i-S242 (42) . A species-specific loop (green) affects the catalytic rate (in PV) (37) . these species matched a poliovirus query, indicating there is greater structural similarity than in other homomorphs and motifs. The N-terminal segment of the homomorph contains some discontinuities that are resolved by using R2R matches for alternative queries ( Figure 5A , lower section). The C-terminal segment of the homomorph is well represented in all RNA polymerases and TERT. No R2R correspondence was found between the residues comprising hmB in the RNA polymerases and residues in the DNA-dependent polymerases (T7 RNAP, N4, TAQ and T7 DNAP).