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* Residue conservation analysis
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PDB id:
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Transcription regulator
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Title:
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Crystal structure of l3mbtl2-h4k20me1 complex
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Structure:
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Lethal(3)malignant brain tumor-like 2 protein. Chain: a, b. Synonym: l(3)mbt-like 2 protein, h-l(3)mbt-like protein. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: l3mbtl2. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.10Å
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R-factor:
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0.203
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R-free:
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0.268
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Authors:
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Y.Guo,C.Qi,A.Allali-Hassani,P.Pan,H.Zhu,A.Dong,F.Mackenzie,L.Crombet, P.Loppnau,I.Kozieradzki,M.Vedadi,A.M.Edwards,J.Weigelt,C.Bountra, C.H.Arrowsmith,A.Botchkarev,R.Read,J.Min,Structural Genomics Consortium (Sgc)
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Key ref:
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Y.Guo
et al.
(2009).
Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.
Nucleic Acids Res,
37,
2204-2210.
PubMed id:
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Date:
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07-Nov-08
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Release date:
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06-Jan-09
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Supersedes:
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PROCHECK
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Headers
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References
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Nucleic Acids Res
37:2204-2210
(2009)
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PubMed id:
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Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.
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Y.Guo,
N.Nady,
C.Qi,
A.Allali-Hassani,
H.Zhu,
P.Pan,
M.A.Adams-Cioaba,
M.F.Amaya,
A.Dong,
M.Vedadi,
M.Schapira,
R.J.Read,
C.H.Arrowsmith,
J.Min.
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ABSTRACT
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The MBT repeat has been recently identified as a key domain capable of
methyl-lysine histone recognition. Functional work has pointed to a role for MBT
domain-containing proteins in transcriptional repression of developmental
control genes such as Hox genes. In this study, L3MBTL2, a human homolog of
Drosophila Sfmbt critical for Hox gene silencing, is demonstrated to
preferentially recognize lower methylation states of several histone-derived
peptides through its fourth MBT repeat. High-resolution crystallographic
analysis of the four MBT repeats of this protein reveals its unique asymmetric
rhomboid architecture, as well as binding mechanism, which preclude the
interaction of the first three MBT repeats with methylated peptides. Structural
elucidation of an L3MBTL2-H4K20me1 complex and comparison with other MBT-histone
peptide complexes also suggests that an absence of distinct surface contours
surrounding the methyl-lysine-binding pocket may underlie the lack of sequence
specificity observed for members of this protein family.
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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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C.Xu,
and
J.Min
(2011).
Structure and function of WD40 domain proteins.
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Protein Cell,
2,
202-214.
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PDB codes:
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H.Honda,
K.Takubo,
H.Oda,
K.Kosaki,
T.Tazaki,
N.Yamasaki,
K.Miyazaki,
K.A.Moore,
Z.Honda,
T.Suda,
and
I.R.Lemischka
(2011).
Hemp, an mbt domain-containing protein, plays essential roles in hematopoietic stem cell function and skeletal formation.
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Proc Natl Acad Sci U S A,
108,
2468-2473.
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M.E.McLaughlin-Drubin,
C.P.Crum,
and
K.Münger
(2011).
Human papillomavirus E7 oncoprotein induces KDM6A and KDM6B histone demethylase expression and causes epigenetic reprogramming.
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Proc Natl Acad Sci U S A,
108,
2130-2135.
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N.Koester-Eiserfunke,
and
W.Fischle
(2011).
H3K9me2/3 binding of the MBT domain protein LIN-61 is essential for Caenorhabditis elegans vulva development.
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PLoS Genet,
7,
e1002017.
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S.P.Rowbotham,
L.Barki,
A.Neves-Costa,
F.Santos,
W.Dean,
N.Hawkes,
P.Choudhary,
W.R.Will,
J.Webster,
D.Oxley,
C.M.Green,
P.Varga-Weisz,
and
J.E.Mermoud
(2011).
Maintenance of Silent Chromatin through Replication Requires SWI/SNF-like Chromatin Remodeler SMARCAD1.
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Mol Cell,
42,
285-296.
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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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K.Liu,
C.Chen,
Y.Guo,
R.Lam,
C.Bian,
C.Xu,
D.Y.Zhao,
J.Jin,
F.MacKenzie,
T.Pawson,
and
J.Min
(2010).
Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain.
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Proc Natl Acad Sci U S A,
107,
18398-18403.
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PDB codes:
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L.Addou-Klouche,
J.Adélaïde,
P.Finetti,
N.Cervera,
A.Ferrari,
I.Bekhouche,
F.Sircoulomb,
C.Sotiriou,
P.Viens,
S.Moulessehoul,
F.Bertucci,
D.Birnbaum,
and
M.Chaffanet
(2010).
Loss, mutation and deregulation of L3MBTL4 in breast cancers.
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Mol Cancer,
9,
213.
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L.Balakrishnan,
and
B.Milavetz
(2010).
Decoding the histone H4 lysine 20 methylation mark.
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Crit Rev Biochem Mol Biol,
45,
440-452.
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M.A.Adams-Cioaba,
Y.Guo,
C.Bian,
M.F.Amaya,
R.Lam,
G.A.Wasney,
M.Vedadi,
C.Xu,
and
J.Min
(2010).
Structural studies of the tandem Tudor domains of fragile X mental retardation related proteins FXR1 and FXR2.
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PLoS One,
5,
e13559.
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PDB codes:
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M.Vedadi,
C.H.Arrowsmith,
A.Allali-Hassani,
G.Senisterra,
and
G.A.Wasney
(2010).
Biophysical characterization of recombinant proteins: a key to higher structural genomics success.
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J Struct Biol,
172,
107-119.
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S.Pu,
A.L.Turinsky,
J.Vlasblom,
T.On,
X.Xiong,
A.Emili,
Z.Zhang,
J.Greenblatt,
J.Parkinson,
and
S.J.Wodak
(2010).
Expanding the landscape of chromatin modification (CM)-related functional domains and genes in human.
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PLoS One,
5,
e14122.
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J.Eryilmaz,
P.Pan,
M.F.Amaya,
A.Allali-Hassani,
A.Dong,
M.A.Adams-Cioaba,
F.Mackenzie,
M.Vedadi,
and
J.Min
(2009).
Structural studies of a four-MBT repeat protein MBTD1.
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PLoS One,
4,
e7274.
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PDB code:
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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.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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}
}
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