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

The extension of all homomorphs from the template tunnel to the exterior of the protein was an unexpected finding. Its universality in the polymerase family suggests a functional significance. Residues within the homomorphs that were localized to the surface often had species-specific loops. The most likely reason these features have not been identified previously is due to the limitations of existing sequence and structure comparison tools-in particular, the ability to perform multi-species comparisons of structures, using overlapping windows of a size determined by the user, and the ability to select the criteria for R2R matches. The homomorphs as defined in this work add structural clarity and context to sequencebased functional motifs previously observed by numerous authors performing comparative studies among polymerases. The structure maps created from the R2R correspondences identified by the StralSV algorithm provided a unique and informative perspective of structure and function in RdRps. They readily identify unique regions of each species and those shared by proteins within a family. These are features that would be useful for studies of any protein family. Based on the results of this study, it may be possible to define characteristic homomorphs for many other protein families, despite considerable sequence variation. It may be feasible to classify homomorphs in a manner analogous to the SCOP database, and in doing so provide new insight into protein evolution.