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The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine-binding site ((SAM)P) also contains a novel pocket ((NS)P) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the (SAM)P-adjoining site holding the nucleotides undergoing methylation ((SUB)P) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2'O and N7 positions, and also displays nucleotide triphosphatase activity.

Original publication

DOI

10.1038/ncomms9749

Type

Journal article

Journal

Nat Commun

Publication Date

09/11/2015

Volume

6

Keywords

Animals, Binding Sites, Chromatography, Thin Layer, Crystallization, Crystallography, X-Ray, Metapneumovirus, Methylation, Mononegavirales, Protein Structure, Tertiary, RNA, RNA Caps, RNA Replicase, S-Adenosylmethionine, Sf9 Cells, Spodoptera, Viral Proteins