Modomics - A Database of RNA Modifications

ID Card:

Full name: tRNA (adenine(57)-N(1)/adenine(58)-N(1))-methyltransferase TrmI
Synonym: pimT-like
GI: 5457862
Orf: PAB0283
COG: COG2519
UniProt: Q9V1J7
Structures: | 3LGA | 3LHD | 3MB5 |
Alpha Fold Predicted Structure: AF-Q9V1J7-F1
Enzyme type: methyltransferase
Position of modification - modification: t:58 - m1A
t:57 - m1I


PDB Structures:


3LGA

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

The S-adenosyl-L-methionine dependent methylation of adenine 58 in the T-loop of tRNAs is essential for cell growth in yeast or for adaptation to high temperatures in thermophilic organisms. In contrast to bacterial and eukaryotic tRNA m(1)A58 methyltransferases that are site-specific, the homologous archaeal enzyme from Pyrococcus abyssi catalyzes the formation of m(1)A also at the adjacent position 57, m(1)A57 being a precursor of 1-methylinosine. We report here the crystal structure of P. abyssi tRNA m(1)A57/58 methyltransferase ((Pab)TrmI), in complex with S-adenosyl-L-methionine or S-adenosyl-L-homocysteine in three different space groups. The fold of the monomer and the tetrameric architecture are similar to those of the bacterial enzymes. However, the inter-monomer contacts exhibit unique features. In particular, four disulfide bonds contribute to the hyperthermostability of the archaeal enzyme since their mutation lowers the melting temperature by 16.5°C. His78 in conserved motif X, which is present only in TrmIs from the Thermococcocales order, lies near the active site and displays two alternative conformations. Mutagenesis indicates His78 is important for catalytic efficiency of (Pab)TrmI. When A59 is absent in tRNA(Asp), only A57 is modified. Identification of the methylated positions in tRNAAsp by mass spectrometry confirms that (Pab)TrmI methylates the first adenine of an AA sequence.

Download RCSB-PDB Structures:

Pdb Files   3LGA.pdb   3LHD.pdb   3MB5.pdb  
Pdbx/mmCIF Files   3LGA.cif   3LHD.cif   3MB5.cif  


Protein sequence:

MIREGDKVVLVDPRGKRYLITVSKRDFHTDLGILKLEEIIGRNFGEAIKSHKGHEFKILRPRIVDYLDKMKRGPQIVHPKDAALIVAYAGISPGDFIVEAGVGSGALTLFLANIVGPEGRVVSYEIREDFAKLAWENIKWAGFDDRVTIKLKDIYEGIEEENVDHVILDLPQPERVVEHAAKALKPGGFFVAYTPCSNQVMRLHEKLREFKDYFMKPRTINVLVFDQEVKKECMRPRTTALVHTGYITFARRI

Comments:

The modified nucleoside 1‐methyladenosine (m1A) is found in the T‐loop of many tRNAs from organisms belonging to the three domains of life (Eukaryota, Bacteria, Archaea). In the T‐loop of eukaryotic and bacterial tRNAs, m1A is present at position 58, whereas in archaeal tRNAs it is present at position(s) 58 and/or 57, m1A57 being the obligatory intermediate in the biosynthesis of 1‐methylinosine (m1I57). In yeast, the formation of m1A58 is catalysed by the essential tRNA (m1A58) methyltransferase (MTase), a tetrameric enzyme that is composed of two types of subunits (Gcd14p and Gcd10p), whereas in the bacterium Thermus thermophilus the enzyme is a homotetramer of the TrmI polypeptide. Here, we report that the TrmI enzyme from the archaeon Pyrococcus abyssi is also a homotetramer. However, unlike the bacterial site‐specific TrmI MTase, the P.abyssi enzyme is region‐specific and catalyses the formation of m1A at two adjacent positions (57 and 58) in the T‐loop of certain tRNAs. The stabilisation of P.abyssi TrmI at extreme temperatures involves intersubunit disulphide bridges that reinforce the tetrameric oligomerisation, as revealed by biochemical and crystallographic evidences. The origin and evolution of m1A MTases is discussed in the context of different hypotheses of the tree of life.




Reaction Substrate SubstrateType Position (Anti)Codon Modified (Anti)Codon Amino Acid Change Transcript Name Transcript Region Cellular Localization References
A:m1A RNA tRNA 58 TΨC-loop Archaeal Cytosol 14739239   
A:m1A RNA tRNA 57 TΨC-loop Archaeal Cytosol 14739239   

Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

M I R E G D K V V L V D P R G K R Y L I T V S K R D F H T D L G I L K L E E I I G R N F G E A I K S H K G H E F K I L R P R I V D Y L D K M K R G P Q I V H P K D A A L I V A Y A G I S P G D F I V E A G V G S G A L T L F L A N I V G P E G R V V S Y E I R E D F A K L A W E N I K W A G F D D R V T I K L K D I Y E G I E E E N V D H V I L D L P Q P E R V V E H A A K A L K P G G F F V A Y T P C S N Q V M R L H E K L R E F K D Y F M K P R T I N V L V F D Q E V K K E C M R P R T T A L V H T G Y I T F A R R I

Secondary Structure Alphabet

  • G: 3-turn helix (310helix)
  • H: α-helix
  • I: 𝝅-helix (5 - turn helix)
  • T: Hydrogen Bonded Turn
  • B: β-sheet
  • S: Bend
  • C: Coil (residues not present in any of the above conformations)
  • N: Not assigned

Download PDB Structures & DSSP Secondary Structures:

Alpha Fold Pdb Files   AF-Q9V1J7-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q9V1J7-F1.cif  
DSSP Secondary Structures   Q9V1J7.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
A primordial RNA modification enzyme: the case of tRNA (m1A) methyltransferase. Roovers M, Wouters J, Bujnicki JM, Tricot C, Stalon V, Grosjean H, Droogmans L Nucleic Acids Res [details] 14739239 -
Structural comparison of tRNA m(1)A58 methyltransferases revealed different molecular strategies to maintain their oligomeric architecture under extreme conditions. Guelorget A, Barraud P, Tisne C, Golinelli-Pimpaneau B BMC Struct Biol [details] 22168821 -
Dynamics of RNA modification by a multi-site-specific tRNA methyltransferase. Hamdane D, Guelorget A, Guerineau V, Golinelli-Pimpaneau B... Nucleic Acids Res [details] 25217588 -
Insights into the hyperthermostability and unusual region-specificity of archaeal Pyrococcus abyssi tRNA m1A57/58 methyltransferase. Guelorget A, Roovers M, Guerineau V, Barbey C, Li X, Golinelli-Pimpaneau B... Nucleic Acids Res [details] 20483913 -