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

We have compared the effects of currently recognized mutations within the motifs and within the homomorphs. Most mutations within the motifs are function-specific, related to either a change in charge or size, and in most cases the mutations are lethal [mA (42) , mB (42) , mC (50), (51) ]. Mutations outside of the motif (but within the homomorph) are more often rate related and located in a segment that bulges from the homomorph by an amount that varies by species (Figures 2A, 3A and 4A ). These differences support the hypothesis that residues actively involved in template processing are essential to viability, and most of them are components of a consistent, stable structure that places and/or maintains them in their appropriate functional position. However, the practice of mutating residues to ala has resulted in a somewhat 'all or nothing' perspective of mutations. StralSV analysis can facilitate informed selection of alternative residues of various compositions, which could possibly affect replication rates to different extents. Experiments involving this type of testing would enhance predictive models and may provide new insights for the design and development of medical countermeasures.