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PDBsum entry 2rje

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protein ligands metals Protein-protein interface(s) links
Transcription PDB id
2rje

 

 

 

 

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Contents
Protein chains
309 a.a. *
Ligands
LYS-ARG-HIS-ARG-
MLY-VAL-LEU-ARG-
ASP
HIS-ARG-MLY-VAL-
LEU-ARG-ASP-ASN
Metals
_CL ×2
Waters ×950
* Residue conservation analysis
PDB id:
2rje
Name: Transcription
Title: Crystal structure of l3mbtl1 in complex with h4k20me2 (residues 17- 25), orthorhombic form ii
Structure: Lethal(3)malignant brain tumor-like protein. Chain: a, b, c. Fragment: residues 200-530. Synonym: l(3)mbt-like, l(3)mbt protein homolog, h-l(3)mbt protein, h- l(3)mbt, l3mbtl1. Engineered: yes. Histone h4. Chain: p, q. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: l3mbtl, kiaa0681, l3mbt. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: synthetic peptide
Resolution:
1.86Å     R-factor:   0.193     R-free:   0.231
Authors: A.Allali-Hassani,Y.Liu,N.Herzanych,H.Ouyang,F.Mackenzie,L.Crombet, P.Loppnau,I.Kozieradzki,M.Vedadi,J.Weigelt,M.Sundstrom, C.H.Arrowsmith,A.M.Edwards,A.Bochkarev,J.R.Min,Structural Genomics Consortium (Sgc)
Key ref:
J.Min et al. (2007). L3MBTL1 recognition of mono- and dimethylated histones. Nat Struct Biol, 14, 1229-1230. PubMed id: 18026117 DOI: 10.1038/nsmb1340
Date:
14-Oct-07     Release date:   30-Oct-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9Y468  (LMBL1_HUMAN) -  Lethal(3)malignant brain tumor-like protein 1 from Homo sapiens
Seq:
Struc:
 
Seq:
Struc:
840 a.a.
309 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1038/nsmb1340 Nat Struct Biol 14:1229-1230 (2007)
PubMed id: 18026117  
 
 
L3MBTL1 recognition of mono- and dimethylated histones.
J.Min, A.Allali-Hassani, N.Nady, C.Qi, H.Ouyang, Y.Liu, F.MacKenzie, M.Vedadi, C.H.Arrowsmith.
 
  ABSTRACT  
 
Crystal structures of the L3MBTL1 MBT repeats in complex with histone H4 peptides dimethylated on Lys20 (H4K20me2) show that only the second of the three MBT repeats can bind mono- and dimethylated histone peptides. Its binding pocket has similarities to that of 53BP1 and is able to recognize the degree of histone lysine methylation. An unexpected mode of peptide-mediated dimerization suggests a possible mechanism for chromatin compaction by L3MBTL1.
 
  Selected figure(s)  
 
Figure 1.
(a) Structure of 3MBT bound to an H4K20me2 peptide (residues 17–25). H4K20me2 peptide is shown in red and the dimethyllysine is shown as a stick model. (b) Sequence alignment of MBT2, MBT1 and MBT3. Red, identical; blue, conserved; dots, lysine-binding pocket residues. (c) Superimposition of the three MBT repeats in 3MBT. Residues forming the lysine-binding pocket are shown as green sticks, and Phe256 from MBT1 and Arg467 from MBT3 are colored pink and blue, respectively. H4K20me2 peptide is shown as yellow sticks.
Figure 2.
(a,b) 3MBT (a, green backbone) and 53BP1 (b, gray backbone). Lysine-binding pocket residues and H4K20me2 peptide are shown as stick models.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2007, 14, 1229-1230) copyright 2007.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23211769 C.A.Musselman, M.E.Lalonde, J.Côté, and T.G.Kutateladze (2012).
Perceiving the epigenetic landscape through histone readers.
  Nat Struct Mol Biol, 19, 1218-1227.  
21468892 C.Xu, and J.Min (2011).
Structure and function of WD40 domain proteins.
  Protein Cell, 2, 202-214.
PDB codes: 3e0c 3fm0 3i2n 3ow8
21252303 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.
  Proc Natl Acad Sci U S A, 108, 2468-2473.  
22120668 K.Acs, M.S.Luijsterburg, L.Ackermann, F.A.Salomons, T.Hoppe, and N.P.Dantuma (2011).
The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks.
  Nat Struct Mol Biol, 18, 1345-1350.  
21243712 P.Voigt, and D.Reinberg (2011).
Histone tails: ideal motifs for probing epigenetics through chemical biology approaches.
  Chembiochem, 12, 236-252.  
20974918 C.Xu, C.Bian, W.Yang, M.Galka, H.Ouyang, C.Chen, W.Qiu, H.Liu, A.E.Jones, F.MacKenzie, P.Pan, S.S.Li, H.Wang, and J.Min (2010).
Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2).
  Proc Natl Acad Sci U S A, 107, 19266-19271.
PDB codes: 3jpx 3jzg 3jzh 3jzn 3k26 3k27
20923397 K.L.Yap, and M.M.Zhou (2010).
Keeping it in the family: diverse histone recognition by conserved structural folds.
  Crit Rev Biochem Mol Biol, 45, 488-505.  
20937909 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.
  Proc Natl Acad Sci U S A, 107, 18398-18403.
PDB codes: 3omc 3omg
20698951 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.
  Mol Cancer, 9, 213.  
20735237 L.Balakrishnan, and B.Milavetz (2010).
Decoding the histone H4 lysine 20 methylation mark.
  Crit Rev Biochem Mol Biol, 45, 440-452.  
20512922 L.M.Congdon, S.I.Houston, C.S.Veerappan, T.M.Spektor, and J.C.Rice (2010).
PR-Set7-mediated monomethylation of histone H4 lysine 20 at specific genomic regions induces transcriptional repression.
  J Cell Biochem, 110, 609-619.  
21072162 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.
  PLoS One, 5, e13559.
PDB codes: 3h8z 3o8v
20466062 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.
  J Struct Biol, 172, 107-119.  
21149733 N.Gurvich, F.Perna, A.Farina, F.Voza, S.Menendez, J.Hurwitz, and S.D.Nimer (2010).
L3MBTL1 polycomb protein, a candidate tumor suppressor in del(20q12) myeloid disorders, is essential for genome stability.
  Proc Natl Acad Sci U S A, 107, 22552-22557.  
21243036 W.P.Janzen, T.J.Wigle, J.Jin, and S.V.Frye (2010).
Epigenetics: Tools and Technologies.
  Drug Discov Today Technol, 7, e59-e65.  
20048137 C.A.Musselman, and T.G.Kutateladze (2009).
PHD fingers: epigenetic effectors and potential drug targets.
  Mol Interv, 9, 314-323.  
19494831 C.Grimm, R.Matos, N.Ly-Hartig, U.Steuerwald, D.Lindner, V.Rybin, J.Müller, and C.W.Müller (2009).
Molecular recognition of histone lysine methylation by the Polycomb group repressor dSfmbt.
  EMBO J, 28, 1965-1977.
PDB code: 3h6z
19891491 F.Liu, X.Chen, A.Allali-Hassani, A.M.Quinn, G.A.Wasney, A.Dong, D.Barsyte, I.Kozieradzki, G.Senisterra, I.Chau, A.Siarheyeva, D.B.Kireev, A.Jadhav, J.M.Herold, S.V.Frye, C.H.Arrowsmith, P.J.Brown, A.Simeonov, M.Vedadi, and J.Jin (2009).
Discovery of a 2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine methyltransferase G9a.
  J Med Chem, 52, 7950-7953.
PDB code: 3k5k
19841675 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.
  PLoS One, 4, e7274.
PDB code: 3feo
19442115 K.S.Champagne, and T.G.Kutateladze (2009).
Structural insight into histone recognition by the ING PHD fingers.
  Curr Drug Targets, 10, 432-441.  
19234526 M.A.Adams-Cioaba, and J.Min (2009).
Structure and function of histone methylation binding proteins.
  Biochem Cell Biol, 87, 93.  
19362589 M.J.Hitchler, and F.E.Domann (2009).
Metabolic defects provide a spark for the epigenetic switch in cancer.
  Free Radic Biol Med, 47, 115-127.  
19184981 P.V.Peña, C.A.Musselman, A.J.Kuo, O.Gozani, and T.G.Kutateladze (2009).
NMR assignments and histone specificity of the ING2 PHD finger.
  Magn Reson Chem, 47, 352-358.  
18923809 S.S.Ng, W.W.Yue, U.Oppermann, and R.J.Klose (2009).
Dynamic protein methylation in chromatin biology.
  Cell Mol Life Sci, 66, 407-422.  
19233876 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, and J.Min (2009).
Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.
  Nucleic Acids Res, 37, 2204-2210.
PDB codes: 3cey 3f70
18250626 A.Edwards (2008).
Bermuda Principles meet structural biology.
  Nat Struct Mol Biol, 15, 116.  
18818090 C.Xu, G.Cui, M.V.Botuyan, and G.Mer (2008).
Structural basis for the recognition of methylated histone H3K36 by the Eaf3 subunit of histone deacetylase complex Rpd3S.
  Structure, 16, 1740-1750.
PDB codes: 2k3x 2k3y
18474616 J.K.Sims, and J.C.Rice (2008).
PR-Set7 establishes a repressive trans-tail histone code that regulates differentiation.
  Mol Cell Biol, 28, 4459-4468.  
18765789 M.Lange, B.Kaynak, U.B.Forster, M.Tönjes, J.J.Fischer, C.Grimm, J.Schlesinger, S.Just, I.Dunkel, T.Krueger, S.Mebus, H.Lehrach, R.Lurz, J.Gobom, W.Rottbauer, S.Abdelilah-Seyfried, and S.Sperling (2008).
Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex.
  Genes Dev, 22, 2370-2384.  
18319261 M.S.Huen, S.M.Sy, J.M.van Deursen, and J.Chen (2008).
Direct interaction between SET8 and proliferating cell nuclear antigen couples H4-K20 methylation with DNA replication.
  J Biol Chem, 283, 11073-11077.  
18538573 N.Nady, J.Min, M.S.Kareta, F.Chédin, and C.H.Arrowsmith (2008).
A SPOT on the chromatin landscape? Histone peptide arrays as a tool for epigenetic research.
  Trends Biochem Sci, 33, 305-313.  
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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