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PMID: 22683997 Published · epublish English Journal Article Research Support, N.I.H., Extramural

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

Nature structural & molecular biology ·Vol. 19 ·No. 7 ·2012-06-10 ·Pages 677-84

Palencia A, Crépin T, Vu MT, Lincecum TL, Martinis SA, Cusack S

Abstract

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.

MeSH Terms
Acylation Biocatalysis Catalytic Domain Crystallography, X-Ray Escherichia coli/enzymology Leucine-tRNA Ligase/chemistry,metabolism Models, Molecular Protein Conformation RNA Editing
Chemicals
Leucine-tRNA Ligase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Palencia Andrés
European Molecular Biology Laboratory (EMBL), Grenoble Outstation and Unit of Virus Host-Cell Interactions, University of Grenoble-EMBL-Centre National de la Recherche Scientifique, Grenoble, France.
Crépin Thibaut
Vu Michael T
Lincecum Tommie L
Martinis Susan A
Cusack Stephen
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2317
Published
2012-06-10
Epub
2012-00-10
Pages
677-84
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3392462
Subset
IM
Grants
NIGMS NIH HHS · R01 GM063789 · United States
NIGMS NIH HHS · GM63789 · United States
Databases
PDB
4AQ7, 4ARC, 4ARI, 4AS1
External Links
PubMed source DOI: 10.1038/nsmb.2317 PMC Full Text View journal details
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