Structural and functional insights into Archaeoglobus fulgidus m2G10 tRNA methyltransferase Trm11 and its Trm112 activator
| Autor: | Can Wang, Nhan van Tran, Marc Graille, Vincent Guérineau, Vincent Jactel |
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| Přispěvatelé: | Laboratoire de Biologie Structurale de la Cellule (BIOC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de synthèse organique (DCSO), École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), ANR-14-CE09-0016,TrMTases,Trm112, un activateur de methyltransférases à l'interface entre la biogenèse du ribosome et sa fonction(2014), Laboratoire Stockage Optique (LSO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA) |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Protein Conformation AcademicSubjects/SCI00010 Archaeal Proteins [SDV]Life Sciences [q-bio] RNA Archaeal [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology 03 medical and health sciences Protein structure RNA Transfer Genetics [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Gene 030304 developmental biology tRNA Methyltransferases 0303 health sciences Molecular Structure Nucleic Acid Enzymes Activator (genetics) 030302 biochemistry & molecular biology Archaeoglobus fulgidus TRNA Methyltransferase Translation (biology) TRNA Methyltransferases Biochemistry Transfer RNA Protein Processing Post-Translational Protein Binding |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 2020, pp.gkaa830. ⟨10.1093/nar/gkaa830⟩ Nucleic Acids Research, Oxford University Press, 2020, 48 (19), pp.11068-11082. ⟨10.1093/nar/gkaa830⟩ Nucleic Acids Research, 2020, 48 (19), pp.11068-11082. ⟨10.1093/nar/gkaa830⟩ |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkaa830 |
| Popis: | tRNAs play a central role during the translation process and are heavily post-transcriptionally modified to ensure optimal and faithful mRNA decoding. These epitranscriptomics marks are added by largely conserved proteins and defects in the function of some of these enzymes are responsible for neurodevelopmental disorders and cancers. Here, we focus on the Trm11 enzyme, which forms N2-methylguanosine (m2G) at position 10 of several tRNAs in both archaea and eukaryotes. While eukaryotic Trm11 enzyme is only active as a complex with Trm112, an allosteric activator of methyltransferases modifying factors (RNAs and proteins) involved in mRNA translation, former studies have shown that some archaeal Trm11 proteins are active on their own. As these studies were performed on Trm11 enzymes originating from archaeal organisms lacking TRM112 gene, we have characterized Trm11 (AfTrm11) from the Archaeoglobus fulgidus archaeon, which genome encodes for a Trm112 protein (AfTrm112). We show that AfTrm11 interacts directly with AfTrm112 similarly to eukaryotic enzymes and that although AfTrm11 is active as a single protein, its enzymatic activity is strongly enhanced by AfTrm112. We finally describe the first crystal structures of the AfTrm11-Trm112 complex and of Trm11, alone or bound to the methyltransferase inhibitor sinefungin. |
| Databáze: | OpenAIRE |
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