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PDBsum entry 3qlc
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Transcription/structural protein
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PDB id
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3qlc
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References listed in PDB file
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Key reference
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Title
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Atrx add domain links an atypical histone methylation recognition mechanism to human mental-Retardation syndrome.
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Authors
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S.Iwase,
B.Xiang,
S.Ghosh,
T.Ren,
P.W.Lewis,
J.C.Cochrane,
C.D.Allis,
D.J.Picketts,
D.J.Patel,
H.Li,
Y.Shi.
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Ref.
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Nat Struct Biol, 2011,
18,
769-776.
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PubMed id
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Abstract
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ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human
congenital disorder that causes severe intellectual disabilities. Mutations in
the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are
responsible for the syndrome. Approximately 50% of the missense mutations in
affected persons are clustered in a cysteine-rich domain termed ADD
(ATRX-DNMT3-DNMT3L, ADD(ATRX)), whose function has remained elusive. Here we
identify ADD(ATRX) as a previously unknown histone H3-binding module, whose
binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine
4 trimethylation (H3K4me3). The cocrystal structure of ADD(ATRX) bound to
H3(1-15)K9me3 peptide reveals an atypical composite H3K9me3-binding pocket,
which is distinct from the conventional trimethyllysine-binding aromatic cage.
Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both
H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we
have discovered a unique histone-recognition mechanism underlying the ATR-X
etiology.
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