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PDBsum entry 2ke1
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Gene regulation
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PDB id
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2ke1
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Gene regulation
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Title:
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Molecular basis of non-modified histone h3 tail recognition by the first phd finger of autoimmune regulator
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Structure:
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Autoimmune regulator. Chain: a. Fragment: first phd domain, unp residues 293-354. Synonym: autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein, apeced protein. Engineered: yes. H3k4me0. Chain: b. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthesized peptide
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NMR struc:
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20 models
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Authors:
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F.Chignola,M.Gaetani,A.Rebane,T.Org,L.Mollica,C.Zucchelli, A.Spitaleri,V.Mannella,P.Peterson,G.Musco
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Key ref:
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F.Chignola
et al.
(2009).
The solution structure of the first PHD finger of autoimmune regulator in complex with non-modified histone H3 tail reveals the antagonistic role of H3R2 methylation.
Nucleic Acids Res,
37,
2951-2961.
PubMed id:
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Date:
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22-Jan-09
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Release date:
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26-May-09
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PROCHECK
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Headers
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References
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O43918
(AIRE_HUMAN) -
Autoimmune regulator from Homo sapiens
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Seq:
Struc:
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545 a.a.
66 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 4 residue positions (black
crosses)
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Nucleic Acids Res
37:2951-2961
(2009)
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PubMed id:
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The solution structure of the first PHD finger of autoimmune regulator in complex with non-modified histone H3 tail reveals the antagonistic role of H3R2 methylation.
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F.Chignola,
M.Gaetani,
A.Rebane,
T.Org,
L.Mollica,
C.Zucchelli,
A.Spitaleri,
V.Mannella,
P.Peterson,
G.Musco.
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ABSTRACT
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Plant homeodomain (PHD) fingers are often present in chromatin-binding proteins
and have been shown to bind histone H3 N-terminal tails. Mutations in the
autoimmune regulator (AIRE) protein, which harbours two PHD fingers, cause a
rare monogenic disease, autoimmune polyendocrinopathy-candidiasis-ectodermal
dystrophy (APECED). AIRE activates the expression of tissue-specific antigens by
directly binding through its first PHD finger (AIRE-PHD1) to histone H3 tails
non-methylated at K4 (H3K4me0). Here, we present the solution structure of
AIRE-PHD1 in complex with H3K4me0 peptide and show that AIRE-PHD1 is a highly
specialized non-modified histone H3 tail reader, as post-translational
modifications of the first 10 histone H3 residues reduce binding affinity. In
particular, H3R2 dimethylation abrogates AIRE-PHD1 binding in vitro and reduces
the in vivo activation of AIRE target genes in HEK293 cells. The observed
antagonism by R2 methylation on AIRE-PHD1 binding is unique among the H3K4me0
histone readers and represents the first case of epigenetic negative cross-talk
between non-methylated H3K4 and methylated H3R2. Collectively, our results point
to a very specific histone code responsible for non-modified H3 tail recognition
by AIRE-PHD1 and describe at atomic level one crucial step in the molecular
mechanism responsible for antigen expression in the thymus.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.A.Musselman,
M.E.Lalonde,
J.Côté,
and
T.G.Kutateladze
(2012).
Perceiving the epigenetic landscape through histone readers.
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Nat Struct Mol Biol,
19,
1218-1227.
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M.S.Anderson,
and
M.A.Su
(2011).
Aire and T cell development.
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Curr Opin Immunol,
23,
198-206.
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P.Slama,
and
D.Geman
(2011).
Identification of family-determining residues in PHD fingers.
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Nucleic Acids Res,
39,
1666-1679.
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S.S.Oliver,
and
J.M.Denu
(2011).
Dynamic interplay between histone H3 modifications and protein interpreters: emerging evidence for a "histone language".
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Chembiochem,
12,
299-307.
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A.S.Koh,
R.E.Kingston,
C.Benoist,
and
D.Mathis
(2010).
Global relevance of Aire binding to hypomethylated lysine-4 of histone-3.
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Proc Natl Acad Sci U S A,
107,
13016-13021.
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H.Hashimoto,
P.M.Vertino,
and
X.Cheng
(2010).
Molecular coupling of DNA methylation and histone methylation.
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Epigenomics,
2,
657-669.
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J.M.Higgins
(2010).
Haspin: a newly discovered regulator of mitotic chromosome behavior.
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Chromosoma,
119,
137-147.
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K.L.Yap,
and
M.M.Zhou
(2010).
Keeping it in the family: diverse histone recognition by conserved structural folds.
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Crit Rev Biochem Mol Biol,
45,
488-505.
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C.A.Musselman,
R.E.Mansfield,
A.L.Garske,
F.Davrazou,
A.H.Kwan,
S.S.Oliver,
H.O'Leary,
J.M.Denu,
J.P.Mackay,
and
T.G.Kutateladze
(2009).
Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications.
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Biochem J,
423,
179-187.
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C.A.Musselman,
and
T.G.Kutateladze
(2009).
PHD fingers: epigenetic effectors and potential drug targets.
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Mol Interv,
9,
314-323.
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J.M.Gardner,
A.L.Fletcher,
M.S.Anderson,
and
S.J.Turley
(2009).
AIRE in the thymus and beyond.
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Curr Opin Immunol,
21,
582-589.
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T.Org,
A.Rebane,
K.Kisand,
M.Laan,
U.Haljasorg,
R.Andreson,
and
P.Peterson
(2009).
AIRE activated tissue specific genes have histone modifications associated with inactive chromatin.
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Hum Mol Genet,
18,
4699-4710.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
