Fig. 4: NiRAN specific recognition of GTP.

a, View of the NiRAN domain of the RTC, bound to GTP, which lies at the amino-terminal end of nsp12. b, GTP is selectively recognized in the NiRAN pocket by a series of hydrogen-bonding and electrostatic interactions in which interacting residues are shown as sticks. c, 2D schematic illustrating the NiRAN-GTP interactions. d, Residues that mediate GTP recognition are shown as sticks and coloured according to their conservation across the α and β coronavirus clades. e, Binding of GTP in the NiRAN is mediated through an induced fit that widens the pocket for insertion of the guanine base. Cross-sections (dashed lines) of the pocket surface area (PSA) of the S4_GTP (GTP bound), S3_UTP and S5_CTP (apo-NiRAN) are shown overlaid on a clipped surface view of the nsp12 NiRAN. The NiRAN pocket volume was measured using the Schrodinger Sitemap tool. The mean ± s.d. of the pocket volumes of the S1_RDV-TP, S3_UTP and S5_CTP structures (apo-NiRAN, n = 3) is shown. The estimated volume sizes of the datasets are shown as overlaid circles in which the green, cyan and red circles represent the calculated PSA for the S3, S5 and S1 structures, respectively.