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…
38 Citations
Methylation of human eukaryotic elongation factor alpha (eEF1A) by a member of a novel protein lysine methyltransferase family modulates mRNA translation
- BiologyNucleic acids research
- 2017
It is demonstrated that an uncharacterized human 7BS MTase currently annotated as part of the endothelin converting enzyme 2, but which should be considered a separate enzyme efficiently methylates K36 in eukaryotic translation elongation factor 1 alpha (eEF1A) in vitro and in vivo.
The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates
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- 2018
The authors identify METTL13 as an eEF1A methyltransferase with dual specificity, which is involved in the codon-specific modulation of mRNA translation.
Novel N-terminal and Lysine Methyltransferases That Target Translation Elongation Factor 1A in Yeast and Human*
- BiologyMolecular & Cellular Proteomics
- 2015
A new eukaryotic protein N-terminal methyltransferase is reported, Saccharomyces cerevisiae YLR285W, which methylates eEF1A at a previously undescribed high-stoichiometry N-Terminal site and the adjacent lysine and is named Efm7.
A new type of protein lysine methyltransferase trimethylates Lys-79 of elongation factor 1A.
- BiologyBiochemical and biophysical research communications
- 2014
The novel lysine specific methyltransferase METTL21B affects mRNA translation through inducible and dynamic methylation of Lys-165 in human eukaryotic elongation factor 1 alpha (eEF1A)
- BiologyNucleic acids research
- 2017
It is demonstrated, using a wide range of in vitro and in vivo approaches, that the previously uncharacterized human methyltransferase METTL21B specifically targets Lys-165 in eEF1A in an aminoacyl-tRNA- and GTP-dependent manner and shows that this modification is dynamic, inducible and likely of regulatory importance.
Evolutionary insights into Trm112-methyltransferase holoenzymes involved in translation between archaea and eukaryotes
- BiologyNucleic acids research
- 2018
It is unraveled that methyltransferases are also privileged Trm112 partners in archaea and that this Trm 112 network is much more complex than anticipated from eukaryotic studies.
Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function
- BiologyNucleic acids research
- 2021
METTL18 is established as the second human histidine-specific protein MTase, and its functional relevance is demonstrated, indicating that METTL18-mediated methylation of RPL3 is important for optimal ribosome biogenesis and function.
Human METTL20 Is a Mitochondrial Lysine Methyltransferase That Targets the β Subunit of Electron Transfer Flavoprotein (ETFβ) and Modulates Its Activity*
- BiologyThe Journal of Biological Chemistry
- 2014
The present study establishes METTL20 as the first human KMT localized to mitochondria and suggests that it may regulate cellular metabolism through modulating the interaction between its substrate ETFβ and dehydrogenases.
METTL21B Is a Novel Human Lysine Methyltransferase of Translation Elongation Factor 1A: Discovery by CRISPR/Cas9 Knockout*
- BiologyMolecular & Cellular Proteomics
- 2017
This is the first study to specifically generate CRISPR/Cas9 knockouts of putative protein methyltransferase genes, for substrate discovery and site mapping, and should prove useful for the discovery of further novel methyltransferases, and more generally for theiscovery of sites for other protein-modifying enzymes.
Found in Translation: The Search for Functional Roles of Translation Elongation Factor Methylation and the Discovery of a Novel Type of Protein Methylation
- Biology
- 2015
This dissertation describes the attempts made to identify this new substrate and modification for protein methylation in Saccharomyces cerevisiae but as of yet, it remains elusive.
References
SHOWING 1-10 OF 61 REFERENCES
Elongation factor methyltransferase 3--a novel eukaryotic lysine methyltransferase.
- Biology, ChemistryBiochemical and biophysical research communications
- 2014
Identification and Characterization of a Novel Human Methyltransferase Modulating Hsp70 Protein Function through Lysine Methylation*
- BiologyThe Journal of Biological Chemistry
- 2013
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.
- BiologyArchives of biochemistry and biophysics
- 2010
A Newly Uncovered Group of Distantly Related Lysine Methyltransferases Preferentially Interact with Molecular Chaperones to Regulate Their Activity
- BiologyPLoS genetics
- 2013
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
- BiologyMolecular microbiology
- 2007
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*
- BiologyThe Journal of Biological Chemistry
- 2010
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.
- BiologyNature communications
- 2012
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
- BiologyMolecular & Cellular Proteomics
- 2003
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.
- Biology, ChemistryThe Biochemical journal
- 2008
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
- BiologyProteomics
- 2012
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.