Protein Domain : RNA synthesis protein NSP10 superfamily, coronavirus IPR036333

Type	Homologous_superfamily
Description	Non-structural protein NSP10 is involved in RNA synthesis. It is synthesised as part of a replicase polyprotein, whose cleavage generates many non-structural proteins [ ]. NSP10 has a mixed α/β fold comprised of five α-helices contains, one 3(10)-helix, and three β-strands () and it is rich in cysteines, featuring two zinc fingers with Cx(2)-C-x(5)-H-x(6)-C and C-x(2)-C-x(7)-C-x-C motifs [ , ]. Twelve identical subunits assemble to form a unique spherical dodecameric architecture, which is proposed to be a functional form of the ExoN/MTase coactivator domainThe small NSP10 protein is among the more conserved coronavirus proteins and a critical cofactor for activation of multiple replicative enzymes. It interacts with NSP14 and NSP16 acting as a scaffolding protein and regulating their respective exonuclease (ExoN) and ribose-2'-O-MTase (2'-O-MTase) activities [, ], mediating the stabilization of the SAM binding pockets of NSP16 and NSP14. When binding to the N-terminal of NSP14, NSP10 allows the ExoN active site to adopt a stably closed conformation, allowing efficient hydrolysis of dsRNA []. Efficient catalytic activity of NSP16 depends on heterodimerization with NSP10. The structure of the SARS-CoV-2 NSP10/NSP16 heterodimer revealed that it is extremely similar to that of its SARS-CoV-1 homologue [].One NSP10 residue, Tyr-96, is of particular interest. The aromatic nature of Tyr-96 plays a crucial role in the NSP10-NSP16 interaction and in the activation of the NSP16 2'-O-MTase activity as well as in the NSP10-NSP14 interaction. This residue is specific for SARS-CoV NSP10, and is a phenylalanine in other coronavirus homologues [ ].
Short Name	NSP10_sf_CoV