Identification and Characterization of a Novel Evolutionarily Conserved Lysine-specific Methyltransferase Targeting Eukaryotic Translation Elongation Factor 2 (eEF2)*

@article{Davydova2014IdentificationAC,
  title={Identification and Characterization of a Novel Evolutionarily Conserved Lysine-specific Methyltransferase Targeting Eukaryotic Translation Elongation Factor 2 (eEF2)*},
  author={Erna Davydova and Angela Yeuan Yen Ho and Jędrzej M. Małecki and Anders Moen and Jorrit M. Enserink and Magnus E. Jakobsson and Christoph Loenarz and P{\aa}l {\O}. Falnes},
  journal={The Journal of Biological Chemistry},
  year={2014},
  volume={289},
  pages={30499 - 30510}
}
Background: The function of many proteins is regulated through post-translational methylation. Results: The previously uncharacterized human methyltransferase FAM86A and its yeast homologue Yjr129c methylate eukaryotic translation elongation factor 2 (eEF2), altering translational frameshifting. Conclusion: Evolutionarily conserved FAM86A methyltransferase modulates the function of eEF2. Significance: The activity of a novel protein-modifying enzyme is discovered and is shown to have functional… 

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References

SHOWING 1-10 OF 61 REFERENCES
Elongation factor methyltransferase 3--a novel eukaryotic lysine methyltransferase.
Identification and Characterization of a Novel Human Methyltransferase Modulating Hsp70 Protein Function through Lysine Methylation*
TLDR
It is shown that trimethylation of HSPA8 (Hsc70) has functional consequences, as it alters the affinity of the chaperone for both the monomeric and fibrillar forms of the Parkinson disease-associated protein α-synuclein.
Two novel methyltransferases acting upon eukaryotic elongation factor 1A in Saccharomyces cerevisiae.
A Newly Uncovered Group of Distantly Related Lysine Methyltransferases Preferentially Interact with Molecular Chaperones to Regulate Their Activity
TLDR
A new role for protein methylation as a regulatory pathway for molecular chaperones is uncovered and a novel regulatory mechanism for the chaperone VCP, whose deregulation is causative of degenerative neuromuscular diseases is defined.
Methylation of proteins involved in translation
TLDR
Differential methylation of specific RPs and TFs in a number of organisms at different physiological states indicates that this modification may play a regulatory role.
A Novel 3-Methylhistidine Modification of Yeast Ribosomal Protein Rpl3 Is Dependent upon the YIL110W Methyltransferase*
TLDR
It is shown that Rpl3, a protein of the large ribosomal subunit from baker's yeast, is stoichiometrically monomethylated at position 243, producing a 3-methylhistidine residue, the first report of a methylated histidine residue in yeast cells, and the first example of a gene required for protein histidine methylation in nature.
Lysine methylation of VCP by a member of a novel human protein methyltransferase family.
TLDR
It is shown that mammalian VCP is trimethylated on Lys315 in a variety of cell lines and tissues, and that the previously uncharacterized protein METTL21D (denoted here as VCP lysine methyltransferase, VCP-KMT) is the responsible enzyme.
Automated Identification of Putative Methyltransferases from Genomic Open Reading Frames*S
TLDR
It is found that simple pattern matching based on the motif sequence is of limited utility and that a new method of “sensitized matrices for scoring methyltransferases” (SM2) produced with modified versions of the MEME and MAST tools gives greatly improved results for the Saccharomyces cerevisiae yeast genome.
The role of the diphthamide-containing loop within eukaryotic elongation factor 2 in ADP-ribosylation by Pseudomonas aeruginosa exotoxin A.
TLDR
It was revealed that the imidazole ring of Diph699 still functions as an ADP-ribose acceptor (albeit poorly), even without the diphthamide modification on the His699, which plays an important role in the ADp-ribosylation of eEF2 catalysed by toxin and also for modification of His699 by the endogenous diphTHamide modification machinery.
Methylation of translation‐associated proteins in Saccharomyces cerevisiae: Identification of methylated lysines and their methyltransferases
TLDR
It is suggested that enzyme YBR271W is named EF methyltransferase 2 (Efm2), in line with the recent naming of YHL039W as Efm1, and lysine methylation was found on the proteins elongation factor (EF) 1‐α, 2, and 3A.
...
1
2
3
4
5
...