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PDBsum entry 3eg6
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protein ligands links
Protein binding PDB id
3eg6

 

 

 

 

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Contents
Protein chain
304 a.a. *
Ligands
ACE-GLY-SER-ALA-
ARG-ALA-GLU-VAL-
HIS-LEU
SO4 ×3
Waters ×287
* Residue conservation analysis
PDB id:
3eg6
Name: Protein binding
Title: Structure of wdr5 bound to mll1 peptide
Structure: Wd repeat-containing protein 5. Chain: a. Fragment: wd-repeat domain (unp residues 23-334). Synonym: bmp2-induced 3-kb gene protein. Engineered: yes. Mll-1 peptide. Chain: c. Fragment: mll-1 win motif. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: wdr5, big3. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence can be naturally found in homo sapiens (human).
Resolution:
1.72Å     R-factor:   0.203     R-free:   0.240
Authors: A.Patel,V.Dharmarajan,M.S.Cosgrove
Key ref:
A.Patel et al. (2008). Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide. J Biol Chem, 283, 32158-32161. PubMed id: 18829459 DOI: 10.1074/jbc.C800164200
Date:
10-Sep-08     Release date:   30-Sep-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P61964  (WDR5_HUMAN) -  WD repeat-containing protein 5 from Homo sapiens
Seq:
Struc: 		334 a.a.
304 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1074/jbc.C800164200 J Biol Chem 283:32158-32161 (2008)
PubMed id: 18829459  
 
 
Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide.
A.Patel, V.Dharmarajan, M.S.Cosgrove.
 
  ABSTRACT  
 
The mixed lineage leukemia protein-1 (MLL1) catalyzes histone H3 lysine 4 methylation and is regulated by interaction with WDR5 (WD-repeat protein-5), RbBP5 (retinoblastoma-binding protein-5), and the Ash2L (absent, small, homeotic discs-2-like) oncoprotein. In the accompanying investigation, we describe the identification of a conserved arginine containing motif, called the "Win" or WDR5 interaction motif, that is essential for the assembly and H3K4 dimethylation activity of the MLL1 core complex. Here we present a 1.7-A crystal structure of WDR5 bound to a peptide derived from the MLL1 Win motif. Our results show that Arg-3765 of MLL1 is bound in the same arginine binding pocket on WDR5 that was previously suggested to bind histone H3. Thermodynamic binding experiments show that the MLL1 Win peptide is preferentially recognized by WDR5. These results are consistent with a model in which WDR5 recognizes Arg-3765 of MLL1, which is essential for the assembly and enzymatic activity of the MLL1 core complex.
 
  Selected figure(s)  
 
Figure 1.
Crystal structure of WDR5 in complex with the MLL1 Win peptide. a, surface representation of WDR5 (magenta) showing the location of MLL1 Win peptide (yellow) bound to the smaller opening at the top of WDR5. b, cutaway view of WDR5 in complex with MLL1 Win peptide showing the location of the 3[10]-helix (yellow ribbon) and the insertion of the Arg-3765 side chain into the central tunnel. 		Figure 4.
Superposition of WDR5 bound to the MLL1 Win peptide (yellow) with that of WDR5 bound to an unmodified histone H3 peptide (white) (PDB code 2CO0, Ref. 17), showing only the bound peptides. Residue names for the MLL1 Win peptide are shown in red, and residue names for the histone H3 peptide are shown in blue. The superposition minimizes the differences between Cα atoms of WDR5 residues between structures.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 32158-32161) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22231400 V.Migliori, J.Müller, S.Phalke, D.Low, M.Bezzi, W.C.Mok, S.K.Sahu, J.Gunaratne, P.Capasso, C.Bassi, V.Cecatiello, A.De Marco, W.Blackstock, V.Kuznetsov, B.Amati, M.Mapelli, and E.Guccione (2012).
Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance.
  Nat Struct Mol Biol, 19, 136-144.
PDB code: 4a7j
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
21220120 V.Avdic, P.Zhang, S.Lanouette, A.Groulx, V.Tremblay, J.Brunzelle, and J.F.Couture (2011).
Structural and biochemical insights into MLL1 core complex assembly.
  Structure, 19, 101-108.
PDB code: 3p4f
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
21124902 F.Cao, Y.Chen, T.Cierpicki, Y.Liu, V.Basrur, M.Lei, and Y.Dou (2010).
An Ash2L/RbBP5 heterodimer stimulates the MLL1 methyltransferase activity through coordinated substrate interactions with the MLL1 SET domain.
  PLoS One, 5, e14102.  
20347844 J.R.England, J.Huang, M.J.Jennings, R.D.Makde, and S.Tan (2010).
RCC1 uses a conformationally diverse loop region to interact with the nucleosome: a model for the RCC1-nucleosome complex.
  J Mol Biol, 398, 518-529.  
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.  
20236310 M.S.Cosgrove, and A.Patel (2010).
Mixed lineage leukemia: a structure-function perspective of the MLL1 protein.
  FEBS J, 277, 1832-1842.  
19897479 P.F.South, I.M.Fingerman, D.P.Mersman, H.N.Du, and S.D.Briggs (2010).
A conserved interaction between the SDI domain of Bre2 and the Dpy-30 domain of Sdc1 is required for histone methylation and gene expression.
  J Biol Chem, 285, 595-607.  
20210320 X.Cheng, and R.M.Blumenthal (2010).
Coordinated chromatin control: structural and functional linkage of DNA and histone methylation.
  Biochemistry, 49, 2999-3008.  
19927323 X.H.Wu, H.Zhang, and Y.D.Wu (2010).
Is Asp-His-Ser/Thr-Trp tetrad hydrogen-bond network important to WD40-repeat proteins: a statistical and theoretical study.
  Proteins, 78, 1186-1194.  
20005892 Y.H.Takahashi, and A.Shilatifard (2010).
Structural basis for H3K4 trimethylation by yeast Set1/COMPASS.
  Adv Enzyme Regul, 50, 104-110.  
19556245 A.Patel, V.Dharmarajan, V.E.Vought, and M.S.Cosgrove (2009).
On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex.
  J Biol Chem, 284, 24242-24256.  
19578375 R.C.Trievel, and A.Shilatifard (2009).
WDR5, a complexed protein.
  Nat Struct Mol Biol, 16, 678-680.  
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 code is shown on the right.

 

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