Identification of a Nidovirales Orf1a N7-guanine cap Methyltransferase signature-sequence as a genetic marker of large genome Tobaniviridae

François Ferron; Humberto Julio Debat; Etienne Decroly; Bruno Canard

The viral 2'-O MTases have been better defined than N7-guanine MTases at the structural and functional level. They all use a K-D-K-E catalytic tetrad, and crystal structures have been determined for several virus groups, such as Reovirus, Flavivirus, Coronavirus, and Mononegavirales (reviewed in [6] , [44] ). All these enzymes (N7-and 2'O-MTase), with SARS-CoV nsp14 as a notable exception (see below), belong to the Rossmann-fold (RF) type MTase (reviewed in [34, 35] ). They bind the methyl donor (SAM), and are characterized by several structural features: their Rossmann fold is a seven-strands β-sheet surrounded with 6 α-helices; the seventh β-strand is inserted in an anti-parallel orientation between the 5th and 6th strand. The SAM cofactor binds to the first structural motif βαβ, which bears the amino acid sequence motif G-x-G-(x) n -G. The RF is an evolutionary ancient fold, which has been widely evolved to perform a variety of chemical reactions. Its structural plasticity is well illustrated by the Flavivirus NS5 MTase, which is able to perform both N7-guanine and 2'-O ribose methylation with the same ~33 kDa domain fused at the N-terminus of the viral RdRp domain [40] .