title: Mechanism of activation of methyltransferases involved in translation by the Trm112 'hub' protein.
abstract: Methylation is a common modification encountered in DNA, RNA and proteins. It plays a central role in gene expression, protein function and mRNA translation. Prokaryotic and eukaryotic class I translation termination factors are methylated on the glutamine of the essential and universally conserved GGQ motif, in line with an important cellular role. In eukaryotes, this modification is performed by the Mtq2-Trm112 holoenzyme. Trm112 activates not only the Mtq2 catalytic subunit but also two other tRNA methyltransferases (Trm9 and Trm11). To understand the molecular mechanisms underlying methyltransferase activation by Trm112, we have determined the 3D structure of the Mtq2-Trm112 complex and mapped its active site. Using site-directed mutagenesis and in vivo functional experiments, we show that this structure can also serve as a model for the Trm9-Trm112 complex, supporting our hypothesis that Trm112 uses a common strategy to activate these three methyltransferases.
authors.affiliation: Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Université Paris-Sud, IFR115, CNRS UMR 8619, Orsay Cedex F-91405, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Liger
authors.forename: Liliana
authors.initials: L
authors.lastname: Mora
authors.forename: Noureddine
authors.initials: N
authors.lastname: Lazar
authors.forename: Sabine
authors.initials: S
authors.lastname: Figaro
authors.forename: Julien
authors.initials: J
authors.lastname: Henri
authors.forename: Nathalie
authors.initials: N
authors.lastname: Scrima
authors.forename: Richard H
authors.initials: RH
authors.lastname: Buckingham
authors.forename: Herman
authors.initials: H
authors.lastname: van Tilbeurgh
authors.forename: Valérie
authors.initials: V
authors.lastname: Heurgué-Hamard
authors.forename: Marc
authors.initials: M
authors.lastname: Graille
mesh_terms: D020134:Catalytic Domain; D003461:Crystallography; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000737:chemistry; D017353:Gene Deletion; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D014176:Protein Biosynthesis; D011496:Protein Methyltransferases / Q000737:chemistry* / Q000235:genetics; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics; D012436:S-Adenosylmethionine / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D012359:tRNA Methyltransferases / Q000235:genetics
chemical_list: D005656:Fungal Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D012436:S-Adenosylmethionine; D011496:Protein Methyltransferases; C480488:TRM9 protein, S cerevisiae; D012359:tRNA Methyltransferases; C502205:Trm112 protein, S cerevisiae