title: Interdomain communication modulates the tRNA-dependent pre-transfer editing of leucyl-tRNA synthetase.
abstract: EcLeuRS [Escherichia coli LeuRS (leucyl-tRNA synthetase)] has evolved both tRNA-dependent pre- and post-transfer editing capabilities to ensure catalytic specificity. Both editing functions rely on the entry of the tRNA CCA tail into the editing domain of the LeuRS enzyme, which, according to X-ray crystal structural studies, leads to a dynamic disordered orientation of the interface between the synthetic and editing domains. The results of the present study show that this tRNA-triggered conformational rearrangement leads to interdomain communication between the editing and synthetic domains through their interface, and this communication mechanism modulates the activity of tRNA-dependent pre-transfer editing. Furthermore, tRNA-dependent editing reaction inhibits misactivating non-cognate amino acids from the synthetic active site. These results also suggested a novel quality control mechanism of EcLeuRS which is achieved through the co-ordination between the synthetic and editing domains.
authors.affiliation: State Key Laboratory of Molecular Biology, Center for RNA Research, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Min
authors.initials: M
authors.lastname: Tan
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.forename: Ru-Juan
authors.initials: RJ
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhou
authors.forename: En-duo
authors.initials: ED
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D007935:Leucine-tRNA Ligase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000235:genetics; D017393:RNA Editing / Q000235:genetics*; D012356:RNA, Transfer, Leu / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D012356:RNA, Transfer, Leu; D007935:Leucine-tRNA Ligase