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2014 ; 426
(20
): 3350-62
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Emerging technologies to map the protein methylome
#MMPMID24805349
Carlson SM
; Gozani O
J Mol Biol
2014[Oct]; 426
(20
): 3350-62
PMID24805349
show ga
Protein methylation plays an integral role in cellular signaling, most notably by
modulating proteins bound at chromatin and increasingly through regulation of
non-histone proteins. One central challenge in understanding how methylation acts
in signaling is identifying and measuring protein methylation. This includes
locus-specific modification of histones, on individual non-histone proteins, and
globally across the proteome. Protein methylation has been studied traditionally
using candidate approaches such as methylation-specific antibodies, mapping of
post-translational modifications by mass spectrometry, and radioactive labeling
to characterize methylation on target proteins. Recent developments have provided
new approaches to identify methylated proteins, measure methylation levels,
identify substrates of methyltransferase enzymes, and match methylated proteins
to methyl-specific reader domains. Methyl-binding protein domains and improved
antibodies with broad specificity for methylated proteins are being used to
characterize the "protein methylome". They also have the potential to be used in
high-throughput assays for inhibitor screens and drug development. These tools
are often coupled to improvements in mass spectrometry to quickly identify
methylated residues, as well as to protein microarrays, where they can be used to
screen for methylated proteins. Finally, new chemical biology strategies are
being used to probe the function of methyltransferases, demethylases, and
methyl-binding "reader" domains. These tools create a "system-level"
understanding of protein methylation and integrate protein methylation into
broader signaling processes.