Fig. 7: Commonalities into allosterically exploiting the RNAP structural flexibility.
From: Structural basis of RNA polymerase inhibition by viral and host factors
a Schematic representation of the conformational changes induced by TFS4 binding. The RNAP is shown in grey, and the part of the structure subjected to conformational change is highlighted in purple with the movement direction indicated by arrows. Main features of RNAP including the secondary channel, jaw, lobe and clamp head, as well as bridge helix and trigger loop are indicated. b Comparison of the archaeal Saci RNAP with eukaryotic RNAPI, II and III and the locations of the ZRC domains of subunits TFS4, RPA12, TFIIS, and RPC10 (human homologous of RPC11) (pdb codes 6rqh, 5xon, and 7ae3, respectively for the eukaryotic factors69,70,31), relative to the rim helices and the active site motifs (aspartate triad, bridge helix and trigger loop). Only the TFS4 ZRC domain is located at the rim of the NTPs-entry funnel and clashes with the trigger loop, while all other ZRC domains reach towards the catalytic magnesium ion (green sphere). c The structural changes associated with the inhibition of the archaeal, bacterial and eukaryotic RNAPI by TFS4, Gfh1, and RNAPI dimerisation, respectively, involve a widening of the DNA binding-channel. The structures of the free, or apo forms of RNAP are shown in dark teal, and the inhibited conformations of the RNAP-TFS4, RNAP-Gfh1 and RNAPI dimers are shown in yellow, respectively. The RNAP clamp helices are highlighted in red and the bridge helix distortions in blue.
