title: Structural comparison of tRNA m(1)A58 methyltransferases revealed different molecular strategies to maintain their oligomeric architecture under extreme conditions.
abstract: BACKGROUND
  tRNA m(1)A58 methyltransferases (TrmI) catalyze the transfer of a methyl group from S-adenosyl-L-methionine to nitrogen 1 of adenine 58 in the T-loop of tRNAs from all three domains of life. The m(1)A58 modification has been shown to be essential for cell growth in yeast and for adaptation to high temperatures in thermophilic organisms. These enzymes were shown to be active as tetramers. The crystal structures of five TrmIs from hyperthermophilic archaea and thermophilic or mesophilic bacteria have previously been determined, the optimal growth temperature of these organisms ranging from 37°C to 100°C. All TrmIs are assembled as tetramers formed by dimers of tightly assembled dimers.
  
  
  RESULTS
  In this study, we present a comparative structural analysis of these TrmIs, which highlights factors that allow them to function over a large range of temperature. The monomers of the five enzymes are structurally highly similar, but the inter-monomer contacts differ strongly. Our analysis shows that bacterial enzymes from thermophilic organisms display additional intermolecular ionic interactions across the dimer interfaces, whereas hyperthermophilic enzymes present additional hydrophobic contacts. Moreover, as an alternative to two bidentate ionic interactions that stabilize the tetrameric interface in all other TrmI proteins, the tetramer of the archaeal P. abyssi enzyme is strengthened by four intersubunit disulfide bridges.
  
  
  CONCLUSIONS
  The availability of crystal structures of TrmIs from mesophilic, thermophilic or hyperthermophilic organisms allows a detailed analysis of the architecture of this protein family. Our structural comparisons provide insight into the different molecular strategies used to achieve the tetrameric organization in order to maintain the enzyme activity under extreme conditions.
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurales, Centre de Recherche de Gif, CNRS, 1 avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Guelorget
authors.forename: Pierre
authors.initials: P
authors.lastname: Barraud
authors.forename: Carine
authors.initials: C
authors.lastname: Tisné
authors.forename: Béatrice
authors.initials: B
authors.lastname: Golinelli-Pimpaneau
mesh_terms: D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology; D020134:Catalytic Domain; D019295:Computational Biology; D018360:Crystallography, X-Ray; D004795:Enzyme Stability; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D043903:Pyrococcus abyssi / Q000201:enzymology; D016415:Sequence Alignment; D013045:Species Specificity; D013696:Temperature; D012359:tRNA Methyltransferases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D012359:tRNA Methyltransferases