Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2′-o-methyltransferase nsp10/nsp16 complex

Cellular and viral s-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism,detoxification,signal transduction,chromatin remodeling,nucleic acid processing,and mrna capping. the severe acute respiratory syndrome coronavirus nsp16 protein is a s-adenosylmethionine-dependent (nucleoside-2′-o)-methyltransferase only active in the presence of its activating partner nsp10. we report the nsp10/nsp16 complex structure at 2.0 å resolution,which shows nsp10 bound to nsp16 through a ~930 å2 surface area in nsp10. functional assays identify key residues involved in nsp10/nsp16 association,and in rna binding or catalysis,the latter likely through a sn2-like mechanism. we present two other crystal structures,the inhibitor sinefungin bound in the s-adenosylmethionine binding pocket and the tighter complex nsp10(y96f)/nsp16,providing the first structural insight into the regulation of rna capping enzymes in (+)rna viruses. © 2011 decroly et al.