Modomics - A Database of RNA Modifications

ID Card:

Full name: tRNA (adenine(58)-N(1))-methyltransferase catalytic subunit TRMT61A
Synonym: C14orf172, TRM61
GI: 123173772
COG: COG2519
UniProt: Q96FX7
Structures: | 5CCB | 5CD1 | 5CCX |
Alpha Fold Predicted Structure: AF-Q96FX7-F1
Complex: Trm6/Trm61
Enzyme type: methyltransferase
Position of modification - modification: t:58 - m1A


PDB Structures:


5CCB

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

Human tRNA3(Lys) is the primer for reverse transcription of HIV; the 3' end is complementary to the primer-binding site on HIV RNA. The complementarity ends at the 18th base, A58, which in tRNA3(Lys) is modified to remove Watson-Crick pairing. Motivated to test the role of the modification in terminating the primer-binding sequence and thus limiting run-on transcription, we asked how the modification of RNA could be accomplished. tRNA m(1)A58 methyltransferase (m(1)A58 MTase) methylates N1 of A58, which is buried in the TΨC-loop of tRNA, from cofactor S-adenosyl-L-methionine. This conserved tRNA modification is essential for stability of initiator tRNA in Saccharomyces cerevisiae. Reported here, three structures of human tRNA m(1)A58 MTase in complex with human tRNA3(Lys) and the product S-adenosyl-L-homocysteine show a dimer of heterodimers in which each heterodimer comprises a catalytic chain, Trm61, and a homologous but noncatalytic chain, Trm6, repurposed as a tRNA-binding subunit that acts in trans; tRNAs bind across the dimer interface such that Trm6 from the opposing heterodimer brings A58 into the active site of Trm61. T-loop and D-loop are splayed apart showing how A58, normally buried in tRNA, becomes accessible for modification. This result has broad impact on our understanding of the mechanisms of modifying internal sites in folded tRNA. The structures serve as templates for design of inhibitors that could be used to test tRNA m(1)A58 MTase's impact on retroviral priming and transcription.

Download RCSB-PDB Structures:

Pdb Files   5CCB.pdb   5CCX.pdb   5CD1.pdb  
Pdbx/mmCIF Files   5CCB.cif   5CCX.cif   5CD1.cif  


Protein sequence:

MSFVAYEELIKEGDTAILSLGHGAMVAVRVQRGAQTQTRHGVLRHSVDLIGRPFGSKVTCGRGGWVYVLHPTPELWTLNLPHRTQILYSTDIALITMMLELRPGSVVCESGTGSGSVSHAIIRTIAPTGHLHTVEFHQQRAEKAREEFQEHRVGRWVTVRTQDVCRSGFGVSHVADAVFLDIPSPWEAVGHAWDALKVEGGRFCSFSPCIEQVQRTCQALAARGFSELSTLEVLPQVYNVRTVSLPPPDLGTGTDGPAGSDTSPFRSGTPMKEAVGHTGYLTFATKTPG

Comments:

A part of heterodimeric Trm6/Trm61 MTase. The activity tested on yeast tRNAs in vitro (tRNAi Met) and on htRNA3Lys expressed in yeast cells in vivo. Paralog of mitochondrial Trm61B.




Reaction Substrate SubstrateType Position (Anti)Codon Modified (Anti)Codon Amino Acid Change Transcript Name Transcript Region Cellular Localization References
A:m1A tRNA (t) Lys/unknown/eukaryotic cytosol 58 16043508   

Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

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

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-Q96FX7-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q96FX7-F1.cif  
DSSP Secondary Structures   Q96FX7.dssp  





Diseases connected to this enzyme:

Description Reaction Disease Name
TRM6/61 regulates the translation of a subset of mRNAs encoding proteins that play role in cancer. A:m1A
Glioblastoma

Publications:

Title Authors Journal Details PubMed Id DOI
The bipartite structure of the tRNA m1A58 methyltransferase from S. cerevisiae is conserved in humans. Ozanick S, Krecic A, Andersland J, Anderson JT RNA [details] 16043508 -
Crystal Structure of the Human tRNA mA58 Methyltransferase-tRNA Complex: Refolding of Substrate tRNA allows Access to the Methylation Target. Finer-Moore J, Czudnochowski N, O'Connell JD 3rd, Wang AL, Stroud RM... J Mol Biol [details] 26470919 -