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PDBsum entry 6b9m
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References listed in PDB file
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Key reference
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Title
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An intramolecular interaction of uhrf1 reveals dual control for its histone association.
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Authors
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L.Gao,
X.F.Tan,
S.Zhang,
T.Wu,
Z.M.Zhang,
H.W.Ai,
J.Song.
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Ref.
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Structure, 2018,
26,
304.
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PubMed id
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Abstract
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UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) is one of the
essential components of mammalian DNA methylation machinery. Chromatin
association of UHRF1 is controlled via an interplay between its intramolecular
interaction and dual recognition of histone H3 trimethylated at lysine 9
(H3K9me3) and hemimethylated DNA. Here, we report the crystal structure of the
N-terminal tandem Tudor domain (TTD) of UHRF1 in complex with the C-terminal
polybasic region (PBR). Structural analysis reveals that PBR binding leads to
displacement of the TTD-plant homeodomain (PHD) linker, as well as blockage of
the H3K9me3-engaging cage, both of which contribute to a chromatin-occluded
UHRF1 conformation. Disruption of the TTD-PBR interaction, which is facilitated
by the binding of UHRF1 to hemimethylated DNA or regulatory protein USP7, shifts
the UHRF1 conformation toward an open state, allowing for efficient H3K9me3
binding. Together, this study provides structural basis for the allosteric
regulation of UHRF1.
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