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

Comparisons of the tertiary structures of the RdRps of 18 viral species indicated that most of the highly conserved residues essential to polymerase function are embedded in large sequence segments that are highly conserved structurally, yet disparate in composition. We have named these conserved segments 'homomorphs' and have identified the composition and length of each homomorph that includes previously recognized polymerase motifs ( Table 2 ). We have demonstrated that the RNA polymerases have structural skeletons (frames) that are highly conserved, with flexible segments between them, and that extensive segments of structure similarity can be identified by the methods we have described. These methods are applicable to the studies of other groups of proteins, and we anticipate that by accessing structure similarity independent of sequence composition, skeletal frameworks will be found in other groups of proteins. Additionally, after structure similarity is identified, differences between members of the group become readily apparent.