RNA helicase module in an acetyltransferase that modifies a specific tRNA anticodon
- 26 March 2009
- journal article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 28 (9), 1362-1373
- https://doi.org/10.1038/emboj.2009.69
Abstract
Post-transcriptional RNA modifications in the anticodon of transfer RNAs frequently contribute to the high fidelity of protein synthesis. In eubacteria, two genome-encoded transfer RNA (tRNA) species bear the same CAU sequence as the anticodons, which are differentiated by modified cytidines at the wobble positions. The elongator tRNA(Met) accepts an acetyl moiety at the wobble base to form N(4)-acetylcytidine (ac(4)C): an inherent modification ensures precise decoding of the AUG codon by strengthening C-G base-pair interaction and concurrently preventing misreading of the near cognate AUA codon. We have determined the crystal structure of tRNA(Met) cytidine acetyltransferase (TmcA) from Escherichia coli complexed with two natural ligands, acetyl-CoA and ADP, at 2.35 A resolution. The structure unexpectedly reveals an idiosyncratic RNA helicase module fused with a GCN5-related N-acetyltransferase (GNAT) fold, which intimately cross-interact. Taken together with the biochemical evidence, we further unravelled the function of acetyl-CoA as an enzyme-activating switch, and propose that an RNA helicase motor driven by ATP hydrolysis is used to deliver the wobble base to the active centre of the GNAT domain.Keywords
This publication has 42 references indexed in Scilit:
- The RNA acetyltransferase driven by ATP hydrolysis synthesizes N4-acetylcytidine of tRNA anticodonThe EMBO Journal, 2008
- tRNA’s Wobble Decoding of the Genome: 40 Years of ModificationJournal of Molecular Biology, 2007
- Structural and functional insights into the human Upf1 helicase coreThe EMBO Journal, 2006
- Snapshots of tRNA sulphuration via an adenylated intermediateNature, 2006
- Mutations in PRP43 That Uncouple RNA-Dependent NTPase Activity and Pre-mRNA Splicing FunctionBiochemistry, 2006
- The DEAD-box protein family of RNA helicasesGene, 2006
- Transfer RNA modification: influence on translational frameshifting and metabolismFEBS Letters, 1999
- The Ras-RasGAP Complex: Structural Basis for GTPase Activation and Its Loss in Oncogenic Ras MutantsScience, 1997
- Enzymatic Formation of Modified Nucleosides in tRNA: Dependence on tRNA ArchitectureJournal of Molecular Biology, 1996
- A novel lysine-substituted nucleoside in the first position of the anticodon of minor isoleucine tRNA from Escherichia coliPure and Applied Chemistry, 1989