A glycine hinge for tRNA-dependent translocation of editing substrates to prevent errors by leucyl-tRNA synthetase

Abstract 

Aminoacyl-tRNA synthetases often rely on a proofreading mechanism to clear mischarging errors before they can be incorporated into newly synthesized proteins. Leucyl-tRNA synthetase (LeuRS) houses a hydrolytic editing pocket in a domain that is distinct from its aminoacylation domain. Mischarged amino acids are transiently translocated ∼30Å between active sites for editing by an unknown tRNA-dependent mechanism. A glycine within a flexible β-strand that links the aminoacylation and editing domains of LeuRS was determined to be important to tRNA translocation. The translocation-defective mutation also demonstrated that the editing site screens both correctly and incorrectly charged tRNAs prior to product release.

Abbreviations: LeuRS, leucyl-tRNA synthetase, CP1, connective polypeptide 1

Keywords: Fidelity, Protein synthesis, Amino acid editing, Translocation