Crystal structure of the SARS-CoV-2 non-structural protein 9, Nsp9

Dene Littler; Benjamin Gully; Rhys N Colson; Jamie Rossjohn

Unexpectedly the high-resolution structure of 3C-Nsp9COV19 diverged from that of the apo-Nsp9COV19 (R.M.S.D 0.86 Å for the monomer and 2.23 Å when superimposing a dimer). The 3C sequence folded-around either side of the paired intersubunit helices to fill two funnel-like hydrophobic cavities (Fig. 2D, 3B, 4C, D) . Namely, 3C residues LEVL, inserted into the opposing cavities either side of the dimer interface and ran parallel to the paired GxxxG motif. Moreover, the 3C sequence formed additional β-sheet interactions with the Nterminus of the protein from the other protomer (Fig. 3B) . To accommodate the 3C residues the N-terminal strand residues moved outward by ~1.6 Å (residues 6-10). This movement allowed the Nterminus to increase the number of β-sheet interactions it formed with β6'. The β-barrel core of the fold remained unchanged but the increase in interactions between β1 and β6' served to exclude the C-terminus, prompting residues 106-111 to condense into a bent extension of the ahelix (Fig. 4A, B) . The subtle structural changes near the interacting GxxxG motifs (Fig. 3D ) are amplified at the periphery of the dimer resulting in ~ 6 Å shift in the β-barrel core (Fig. 4C)