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

All of the homomorphs included residues that connect the template tunnel or the NTP entry tunnel with the outer surface of the protein. Although some of the surface residues within these homomorphs have specific functional roles, as reported in the literature (see citations in previous paragraphs), we anticipate that they may all be important for polymerase function; the consistent occurrence of homomorphs embedding motifs-even when a defined sequence motif is small in size-suggests a structurefunction relationship between the motif and its structurally conserved flanking regions. It would be interesting to explore the possibility that interactions at the surface of the protein (e.g. protein-protein contact at surface homomorph residues) may subtly affect function buried deep beneath, within the tunnel. Furthermore, each homomorph is either divided by or is separated from another homomorph by a flexible secondary structure. Identification of the span of each homomorph and the terminal residue enables us to identify specific residues on the surface that would not, in many cases, be otherwise noticed. By comparing experimental data with the surface location of the ends of the homomorphs, we have found that these are often the sites of key functional interactions of the protein. A paper describing these sites is in preparation.