Structural comparison of tRNA m1A58 methyltransferases revealed different molecular strategies to maintain their oligomeric architecture under extreme conditions
1 Laboratoire d'Enzymologie et Biochimie Structurales, Centre de Recherche de Gif, CNRS, 1 avenue de la Terrasse, 91190 Gif-sur-Yvette, France
2 CNRS, UMR 8015, Laboratoire de Cristallographie et RMN biologiques, 4 avenue de l'Observatoire 75006 Paris, France
3 Université Paris Descartes, Sorbonne Paris Cité, UMR 8015, Laboratoire de Cristallographie et RMN biologiques, 4 avenue de l'Observatoire 75006 Paris, France
4 Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zürich, Switzerland
BMC Structural Biology 2011, 11:48 doi:10.1186/1472-6807-11-48Published: 14 December 2011
tRNA m1A58 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 m1A58 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.
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.
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.