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The Highly Conserved KEOPS/EKC Complex is Essential for a Universal TRNA Modification, T6A

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Journal EMBO J
Date 2010 Dec 25
PMID 21183954
Citations 110
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Abstract

The highly conserved Kinase, Endopeptidase and Other Proteins of small Size (KEOPS)/Endopeptidase-like and Kinase associated to transcribed Chromatin (EKC) protein complex has been implicated in transcription, telomere maintenance and chromosome segregation, but its exact function remains unknown. The complex consists of five proteins, Kinase-Associated Endopeptidase (Kae1), a highly conserved protein present in bacteria, archaea and eukaryotes, a kinase (Bud32) and three additional small polypeptides. We showed that the complex is required for a universal tRNA modification, threonyl carbamoyl adenosine (t6A), found in all tRNAs that pair with ANN codons in mRNA. We also showed that the bacterial ortholog of Kae1, YgjD, is required for t6A modification of Escherichia coli tRNAs. The ATPase activity of Kae1 and the kinase activity of Bud32 are required for the modification. The yeast protein Sua5 has been reported previously to be required for t6A synthesis. Using yeast extracts, we established an in vitro system for the synthesis of t6A that requires Sua5, Kae1, threonine, bicarbonate and ATP. It remains to be determined whether all reported defects of KEOPS/EKC mutants can be attributed to the lack of t6A, or whether the complex has multiple functions.

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References
1.
Koonin E . New variants of known folds: do they bring new biology?. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010; 66(Pt 10):1226-9. PMC: 2954209. DOI: 10.1107/S1744309110013242. View

2.
Peggion C, Lopreiato R, Casanova E, Ruzzene M, Facchin S, Pinna L . Phosphorylation of the Saccharomyces cerevisiae Grx4p glutaredoxin by the Bud32p kinase unveils a novel signaling pathway involving Sch9p, a yeast member of the Akt / PKB subfamily. FEBS J. 2008; 275(23):5919-33. DOI: 10.1111/j.1742-4658.2008.06721.x. View

3.
Aravind L, Koonin E . Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches. J Mol Biol. 1999; 287(5):1023-40. DOI: 10.1006/jmbi.1999.2653. View

4.
Lopreiato R, Facchin S, Sartori G, Arrigoni G, Casonato S, Ruzzene M . Analysis of the interaction between piD261/Bud32, an evolutionarily conserved protein kinase of Saccharomyces cerevisiae, and the Grx4 glutaredoxin. Biochem J. 2003; 377(Pt 2):395-405. PMC: 1223863. DOI: 10.1042/BJ20030638. View

5.
Hecker A, Lopreiato R, Graille M, Collinet B, Forterre P, Libri D . Structure of the archaeal Kae1/Bud32 fusion protein MJ1130: a model for the eukaryotic EKC/KEOPS subcomplex. EMBO J. 2009; 27(17):2340-51. PMC: 2529370. DOI: 10.1038/emboj.2008.157. View