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PDBsum entry 5f5e
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References listed in PDB file
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Key reference
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Title
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Structural basis for activity regulation of mll family methyltransferases.
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Authors
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Y.Li,
J.Han,
Y.Zhang,
F.Cao,
Z.Liu,
S.Li,
J.Wu,
C.Hu,
Y.Wang,
J.Shuai,
J.Chen,
L.Cao,
D.Li,
P.Shi,
C.Tian,
J.Zhang,
Y.Dou,
G.Li,
Y.Chen,
M.Lei.
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Ref.
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Nature, 2016,
530,
447-452.
[DOI no: ]
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PubMed id
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Abstract
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The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A
and SET1B) specifically methylate histone 3 Lys4, and have pivotal roles in the
transcriptional regulation of genes involved in haematopoiesis and development.
The methyltransferase activity of MLL1, by itself severely compromised, is
stimulated by the three conserved factors WDR5, RBBP5 and ASH2L, which are
shared by all MLL family complexes. However, the molecular mechanism of how
these factors regulate the activity of MLL proteins still remains poorly
understood. Here we show that a minimized human RBBP5-ASH2L heterodimer is the
structural unit that interacts with and activates all MLL family histone
methyltransferases. Our structural, biochemical and computational analyses
reveal a two-step activation mechanism of MLL family proteins. These findings
provide unprecedented insights into the common theme and functional plasticity
in complex assembly and activity regulation of MLL family methyltransferases,
and also suggest a universal regulation mechanism for most histone
methyltransferases.
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