Disulfide-directed histone ubiquitylation reveals plasticity in hDot1L activation.
We have developed a readily accessible disulfide-directed methodology for the site-specific modification of histones by ubiquitin and ubiquitin-like proteins. The disulfide-linked analog of mono-ubiquitylated H2B stimulated the H3K79 methyltransferase activity of hDot1L to a similar extent as the native isopeptide linkage. This permitted structure-activity studies of ubiquitylated mononucleosomes that revealed plasticity in the mechanism of hDot1L stimulation and identified surfaces of ubiquitin important for activation.
Chatterjee
Champak
C
Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York, USA.
McGinty
Robert K
RK
Fierz
Beat
B
Muir
Tom W
TW
D004220:Disulfides / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination; D014452:Ubiquitins / Q000378:metabolism
D004220:Disulfides; D006657:Histones; D025801:Ubiquitin; D014452:Ubiquitins; C473477:DOT1L protein, human; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase