Structural dynamics of the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase

Nat Struct Mol Biol. 2012 Jun 10;19(7):677-84. doi: 10.1038/nsmb.2317.


Leucyl-tRNA synthetase (LeuRS) produces error-free leucyl-tRNA(Leu) by coordinating translocation of the 3' end of (mis-)charged tRNAs from its synthetic site to a separate proofreading site for editing. Here we report cocrystal structures of the Escherichia coli LeuRS-tRNA(Leu) complex in the aminoacylation or editing conformations, showing that translocation involves correlated rotations of four flexibly linked LeuRS domains. This pivots the tRNA to guide its charged 3' end from the closed aminoacylation state to the editing site. The editing domain unexpectedly stabilizes the tRNA during aminoacylation, and a large rotation of the leucine-specific domain positions the conserved KMSKS loop to bind the 3' end of the tRNA, promoting catalysis. Our results give new insight into the structural dynamics of a molecular machine that is essential for accurate protein synthesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acylation
  • Biocatalysis
  • Catalytic Domain
  • Crystallography, X-Ray
  • Escherichia coli / enzymology*
  • Leucine-tRNA Ligase / chemistry
  • Leucine-tRNA Ligase / metabolism*
  • Models, Molecular
  • Protein Conformation
  • RNA Editing


  • Leucine-tRNA Ligase

Associated data

  • PDB/4AQ7
  • PDB/4ARC
  • PDB/4ARI
  • PDB/4AS1