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

Structural examination of the sequence motif regions yielded extended regions of structural conservation. We named each of these regions a 'homomorph', defined as a sequence segment that shares a highly similar tertiary structure with other species, independent of the sequence composition. We found that most of the homomorphs were at least twice as long as the corresponding sequence motif. The extent of this expansion is illustrated in Figure 1 . The length of each homomorph was determined separately for each species, using a single structure for each species as the query in a StralSV analysis. The identity of the start and end of each homomorph depends on the structural similarity to a given query. Therefore, there is some minor query-specific variability of the location of the ends of homomorphs that can be observed in Figure 1 . Within the homomorphs, non-matching residues can be used to identify minor differences between species. In most single-stranded RdRp (ss-RdRp) species (PV, COXS, HRV, FMDV, NV, RHDV, SAPV, HCV, BVDV, WN and DENV), the homomorphs of Motif G are the largest (median of 53 residues), followed by A (49), B (46), E (37), F3 (28), D (23), C (17), F1 (10) and F2 (8) . In double-stranded RdRps (ds-RdRps) (PHI6, REOV, ROTAV, IBDV and IPNV), the homomorphs of Motif G are relatively short (median of 12 residues). Several other homomorphs are also shorter in ds-RdRps: B (48), A (41), E (31), F3 (28), D (16), C (12), F1 (11) and F2 (2) . The lengths and occurrences of homomorphs of polymerases that are associated with DNA (HIV, TERT, TAQ, T7 DNAP, T7 RNAP and N4) are variable and will be discussed in the sections describing each motif.