A Structure-Function Diversity Survey of the RNA-Dependent RNA Polymerases From the Positive-Strand RNA Viruses

Jia, Hengxia; Gong, Peng

With the assignment of the key motifs and the size estimation between these motifs and boundaries of the catalytic module, we are able to predict whether functional regions exist at both N-and C-terminal sides of the catalytic module and the approximate size of these regions using the aforementioned criterion, in particular, for those RdRPs with defined boundaries. Interestingly, most of these additional functional regions with an estimated size of 100 residues or larger were found at the N-terminal side of the catalytic module (14 out of 30 families with defined N-terminus), while much fewer showed up at the C-terminal side (4 out of 37 families with defined C-terminus) (Figure 1) . The preference of "recruiting" N-terminal regions may be related to two factors. Firstly, among all 46 virus families surveyed, 22 families have the RdRP coding region located at the 3 -end of a polyprotein open reading frame (ORF), while 16 families have the RdRP coding region in the middle of an ORF and 8 families have the RdRP coding region as an independent ORF. Secondly, the de novo RdRPs tend to have important initiation elements located at its C-terminus (e.g., the aforementioned priming FIGURE 3 | Global views of seven representative RdRPs 3D structures. RdRP structures are shown in cartoon representations. If available, order/family/genus/species assignments are shown on top of each structure. PV, poliovirus, PDB entry 1RA6 (chain A); NV, norovirus, PDB entry 1SH0 (chain A); Qβ, bacteriophage Qβ, PDB entry 3MMP (chain G); TaV, Thosea asigna virus, PDB entry 4XHI (chain A); HCV, hepatitis C virus, PDB entry 1C2P (chain A); JEV, Japanese encephalitis virus, PDB entry 4K6M (chain A); CSFV, classical swine fever virus, PDB entry 5YF5 (chain A). Coloring scheme: RdRP palm in gray, thumb in blue, fingers in pink, and signature sequence XGDD in magenta. The α-carbon atom of the three absolutely conserved amino acid residues (labeled by asterisks in Figure 2 ) are shown as green spheres. The N-terminal additional regions, if present, are shown in cyan.