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

Residues within hmD perform varied functions. In PV, e.g. polymerases form an extensive lattice system by polymerase-polymerase interactions; L342 and D349, located within hmD, contribute to interface I of this lattice system (53) . The most highly conserved residue within the homomorph is a gly (PV G351) at the N-terminal edge of the motif and central to the homomorph; gly in this position would facilitate the folding of the homomorph, and is consistent with Cameron et al.'s (40) hypothesis that Motif D may be the most dynamic structural element of RdRps and RTs. Another conserved residue is a lys near the C-terminal edge (PV-K359). Residues equivalent to PV-K359 supply a proton to the nucleotidyl transfer reaction that increases the rate constant for nucleotide addition by 50-to 1000-fold (40) . In PV, within the motif, the insertion T353-t-M354 results in small plaques, likely due to delayed RNA synthesis (54) . In other homomorphs, mutations that affect the rate of synthesis occur more commonly outside of the motifs. Immediately downstream from the homomorph, PV-T362I is an attenuating mutation for the Sabin vaccine (40) .