Fig. 2. Structural architecture of the hPIV3 L protein.

a The RdRp domain is shown in ribbons, with the fingers subdomain in blue, the palm subdomain in red, the thumb subdomain in dark green, and the N-terminal region (NTD) in gray. The catalytic residues 772-GDN-774 and the magnesium ion (Mg²⁺) at the active site are shown as sticks and sphere, respectively. b Motifs A–G of the RdRp domain are highlighted in rainbow colors with the same view as in (a). c, d RdRp active site. The RdRp domain of hPIV3 is superimposed on that of RNA duplex/Mg²⁺-bound RdRp structures of FluB (PDB 6QCX) (c) and SARS-CoV-2 (PDB 7BV2) (d). Motifs A–G are labeled as A–G. The hPIV3 structure is colored in aquamarine, while FluB and SARS-CoV-2 structures are colored in gray except for the template and primer (product) strand RNAs in light orange and marine blue, respectively. The nucleotide at the +1 position of the primer strand and the pyrophosphate (PPi) are shown as sticks. The catalytic residues and critical conserved residues that interact with RNA are also shown as sticks. e The PRNTase domain (green) of hPIV3 L. A superposition of hPIV3 L with VSV L (PDB 6U1X) (gray) highlights the conformational differences of the putative priming loops and intrusion loops. The priming loops of hPIV3 and VSV are colored in claret and pink, respectively, while intrusion loops are in blue and black, respectively. The disordered region of hPIV3 intrusion loop is shown as a dotted line. The conserved GxxT motif and HR motif are labeled. The hPIV3 RdRp domain is shown as aquamarine surface. The red star indicates the RdRp active site. f Superposition of CD-MTase-CTD of hPIV3 (yellow-orange-red) and PIV5 (PDB 6V85) (similar colors). RdRp-PRNTase of hPIV3 is shown as transparent surface. The disordered regions of the loops are shown as dotted lines. Potential steric clash between PIV5 priming loop and the CD adopting the same conformation as hPIV3 is indicated by red dashes. Movements are indicated by arrows. The β-strand latch (Phe641–Lys644) of hPIV3 L RdRp is labeled.