The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure

Martin, Baptiste; Coutard, Bruno; Guez, Théo; Paesen, Guido C; Canard, Bruno; Debart, Françoise; Vasseur, Jean-Jacques; Grimes, Jonathan M; Decroly, Etienne

The L protein of mononegaviruses is a multi-functional protein. Although it varies in length, sequence analysis re-vealed that L protein contains six conserved regions (CRI to CRVI, Figure 1A ) (9) . To date, the only available structure of a complete L protein from a mononegavirus is that of VSV. The structure, determined by cryo-electron microscopy, revealed a topological organization in five domains (10) to which distinct functions were attributed. These are, from N-to the C-terminus ( Figure 1A) : the RNA-dependent RNA polymerase (RdRp) closely associated with a capping domain (Cap) containing polyribonucleotidyltransferase (PRNTase) activity, a structured connector domain (CD), the methyltransferase domain (MTase) and a small C-terminal domain (CTD). The enzymatic activities of the L protein are crucial for virus replication. Indeed, the RdRp domain drives genome replication and transcription into mRNAs (11) , the PRNTase appends the cap structure onto the 5 end of the viral transcripts (12) (13) (14) (15) (16) (17) (18) and the MTase is involved in methylation of the cap (19) (20) (21) (22) (23) .