The winding path of protein methylation research: milestones and new frontiers

@article{Murn2017TheWP,
  title={The winding path of protein methylation research: milestones and new frontiers},
  author={Jernej Murn and Yang Shi},
  journal={Nature Reviews Molecular Cell Biology},
  year={2017},
  volume={18},
  pages={517-527}
}
  • J. Murn, Yang Shi
  • Published 17 May 2017
  • Biology, Medicine
  • Nature Reviews Molecular Cell Biology
In 1959, while analysing the bacterial flagellar proteins, Ambler and Rees observed an unknown species of amino acid that they eventually identified as methylated lysine. Over half a century later, protein methylation is known to have a regulatory role in many essential cellular processes that range from gene transcription to signal transduction. However, the road to this now burgeoning research field was obstacle-ridden, not least because of the inconspicuous nature of the methyl mark itself… Expand
Exceptionally versatile – arginine in bacterial post-translational protein modifications
TLDR
This review will discuss how bacteria control their cellular processes and develop pathogenicity based on post-translational protein-arginine modifications. Expand
Post-translational modification of nucleoid-associated proteins: an extra layer of functional modulation in bacteria?
TLDR
Proteome mass spectrometry data for PTMs of the four most abundantly present NAPs in Escherichia coli are scrutinized to identify 101 unique PTMs, and potential effects of these modifications (perturbed DNA-binding, structural integrity or interaction with other proteins) on their function are described. Expand
METTL18-mediated histidine methylation on RPL3 modulates translation elongation for proteostasis maintenance
TLDR
It is reported that human METTL18 is a histidine methyltransferase for the ribosomal protein RPL3 and that the modification specifically slows ribosome traverse on tyrosine codons, allowing the proper folding of synthesized proteins. Expand
An outlook on lysine methylation of non-histone proteins in plants
TLDR
The plant enzymes involved in the methylation of non-histone substrates are described, historical and recent advances in the identification are considered, and current knowledge about the role of protein lysine methylation in regulating molecular and cellular functions in plants is discussed. Expand
Eukaryote-Conserved Methylarginine Is Absent in Diplomonads and Functionally Compensated in Giardia
TLDR
The results challenge the view that arginine methylation is eukaryote conserved and demonstrate that functional compensation of methylarginine was possible preceding expansion and diversification of these key networks in higher eUKaryotes. Expand
Engineering Methyllysine Writers and Readers for Allele-Specific Regulation of Protein-Protein Interactions.
TLDR
This approach provides an unprecedented strategy for specific manipulation of the methyllysine interactome and establishes biochemical integrity of the engineered interface, structural evidence for orthogonality and its applicability to identify transcriptional regula-tors. Expand
Lysine Methylation Regulators Moonlighting outside the Epigenome.
TLDR
Recent discoveries implicating non-histone lysine methylation as a major regulator of diverse cellular processes are summarized and shaping the understanding of the fundamental mechanisms of non- histone protein regulation through this dynamic and multi-functional posttranslational modification. Expand
Targeting protein methylation: from chemical tools to precision medicines
TLDR
This review presents general principles for drugging protein methyltransferases or their downstream effectors containing methyl-binding modules, as well as best-in-class examples of the compounds discovered and their impact both at the bench and in the clinic. Expand
Isolation and Identification of Protein l-Isoaspartate-O-Methyltransferase (PIMT) Interacting Proteins in Salmonella Typhimurium
TLDR
The findings were supported by alterations in secondary structure of the proteins upon co-incubation and the enzyme was also found to be crucial for survival, virulence and colonization of ST in poultry. Expand
Lysine Methyltransferases Signaling: Histones are Just the Tip of the Iceberg.
TLDR
The exploration of the "methylome network" raises the possibility of using SET- and 7β-strand- containing human lysine methyltransferases and their substrates as promising new therapeutic targets for the development of future epigenetic and methyllysine signaling cancer treatments. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 166 REFERENCES
Protein arginine methylation: Cellular functions and methods of analysis.
TLDR
Recent methods and findings that have yielded new insights into the cellular functions of arginine-methylated proteins are described and the currently used procedures for the detection and analysis ofArginine methylation are evaluated. Expand
Deciphering arginine methylation: Tudor tells the tale
TLDR
Tudor proteins are now known to be present in PIWI complexes, where they are thought to interact with methylated PIWI proteins and regulate the PIWI-interacting RNA (piRNA) pathway in the germ line. Expand
Selective Inhibitors of Protein Methyltransferases
TLDR
A perspective on selective, small-molecule inhibitors of PMTs with an emphasis on their discovery, characterization, and applicability as chemical tools for deciphering the target PMTs’ physiological functions and involvement in human diseases is presented. Expand
Molecular Recognition of Lys and Arg Methylation.
TLDR
The physical organic concepts that drive the molecular recognition of Lys and Arg methylation by reader proteins are outlined and comparisons to the binding mechanisms of small molecule receptors for methylated Lys andArg that have been developed recently are drawn. Expand
The structure and oligomerization of the yeast arginine methyltransferase, Hmt1
TLDR
The crystal structure of Hmt1 is reported, which forms a hexamer with approximate 32 symmetry, dominated by large acidic cavities at the dimer interfaces and Mutating residues in the acidic cavity significantly reduces binding and methylation of the substrate Npl3. Expand
Protein lysine methyltransferase G9a acts on non-histone targets.
TLDR
Using the specificity profile of the protein methyltransferase G9a, new non-histone protein targets are identified, including CDYL1, WIZ, ACINUS and G 9a (automethylation), as well as peptides derived from CSB, to demonstrate potential downstream signaling pathways for methylation of non- histone proteins. Expand
Structure of the Neurospora SET Domain Protein DIM-5, a Histone H3 Lysine Methyltransferase
TLDR
The crystal structure of Neurospora DIM-5, a histone H3 lysine 9 methyltranferase (HKMT), determined at 1.98 A resolution, suggests a mechanism for the methylation reaction and provides the structural basis for functional characterization of the HKMT family and the SET domain. Expand
ɛ-N-Methyl-lysine in Bacterial Flagellar Protein
FLAGELLAR proteins (flagellins) from several species of bacteria have been studied by Weibull1 and, more recently, by Koffler2. The present investigations have revealed differences in the amino-acidExpand
A proteomic approach for the identification of novel lysine methyltransferase substrates
TLDR
A novel proteome-wide methodology for the identification of new PKMT substrates is described, which may lead to a better understanding of the enzymatic activity and substrate specificity of the large number of PKMTs present in the human proteome, most of which are uncharacterized. Expand
Structure and Catalytic Mechanism of a SET Domain Protein Methyltransferase
TLDR
It is proposed that methyl transfer is catalyzed by a conserved Tyr at a narrow pore connecting the sites of protein lysine methylation, promoting highly specific protein recognition and allowing addition of multiple methyl groups. Expand
...
1
2
3
4
5
...