The tRNA-induced conformational activation of human mitochondrial phenylalanyl-tRNA synthetase

Structure. 2008 Jul;16(7):1095-104. doi: 10.1016/j.str.2008.03.020.


All class II aminoacyl-tRNA synthetases (aaRSs) are known to be active as functional homodimers, homotetramers, or heterotetramers. However, multimeric organization is not a prerequisite for phenylalanylation activity, as monomeric mitochondrial phenylalanyl-tRNA synthetase (PheRS) is also active. We herein report the structure, at 2.2 A resolution, of a human monomeric mitPheRS complexed with Phe-AMP. The smallest known aaRS, which is, in fact, 1/5 of a cytoplasmic analog, is a chimera of the catalytic module of the alpha and anticodon binding domain (ABD) of the bacterial beta subunit of (alphabeta)2 PheRS. We demonstrate that the ABD located at the C terminus of mitPheRS overlaps with the acceptor stem of phenylalanine transfer RNA (tRNAPhe) if the substrate is positioned in a manner similar to that seen in the binary Thermus thermophilus complex. Thus, formation of the PheRS-tRNAPhe complex in human mitochondria must be accompanied by considerable rearrangement (hinge-type rotation through approximately 160 degrees) of the ABD upon tRNA binding.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / chemistry
  • Amino Acid Sequence
  • Amino Acyl-tRNA Synthetases / chemistry
  • Enzyme Activation
  • Humans
  • Mitochondrial Proteins / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Phenylalanine-tRNA Ligase / chemistry*
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Transfer, Phe / chemistry*
  • Sequence Homology, Amino Acid


  • Mitochondrial Proteins
  • RNA, Transfer, Phe
  • Adenosine Monophosphate
  • phenylalanyl-5'-AMP
  • Amino Acyl-tRNA Synthetases
  • Phenylalanine-tRNA Ligase

Associated data

  • PDB/3CMQ