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PDBsum entry 2ku7

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protein links
Transcription PDB id
2ku7
Jmol
Contents
Protein chain
140 a.a. *
* Residue conservation analysis
PDB id:
2ku7
Name: Transcription
Title: Solution structure of mll1 phd3-cyp33 rrm chimeric protein
Structure: Mll1 phd3-cyp33 rrm chimeric protein. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: J.Song,Z.Wang,D.Patel
Key ref: Z.Wang et al. (2010). Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression. Cell, 141, 1183-1194. PubMed id: 20541251 DOI: 10.1016/j.cell.2010.05.016
Date:
12-Feb-10     Release date:   07-Jul-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q03164  (MLL1_HUMAN) -  Histone-lysine N-methyltransferase 2A
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
3969 a.a.
140 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9UNP9  (PPIE_HUMAN) -  Peptidyl-prolyl cis-trans isomerase E
Seq:
Struc:
301 a.a.
140 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 93 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: E.C.2.1.1.43  - Histone-lysine N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N6-methyl-L-lysine-[histone]
S-adenosyl-L-methionine
+ L-lysine-[histone]
= S-adenosyl-L-homocysteine
+ N(6)-methyl-L-lysine-[histone]
   Enzyme class 2: E.C.5.2.1.8  - Peptidylprolyl isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Peptidylproline (omega=180) = peptidylproline (omega=0)
Peptidylproline (omega=180)
= peptidylproline (omega=0)
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     nucleotide binding     2 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.cell.2010.05.016 Cell 141:1183-1194 (2010)
PubMed id: 20541251  
 
 
Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression.
Z.Wang, J.Song, T.A.Milne, G.G.Wang, H.Li, C.D.Allis, D.J.Patel.
 
  ABSTRACT  
 
The MLL1 gene is a frequent target for recurrent chromosomal translocations, resulting in transformation of hematopoietic precursors into leukemia stem cells. Here, we report on structure-function studies that elucidate molecular events in MLL1 binding of histone H3K4me3/2 marks and recruitment of the cyclophilin CyP33. CyP33 contains a PPIase and a RRM domain and regulates MLL1 function through HDAC recruitment. We find that the PPIase domain of CyP33 regulates the conformation of MLL1 through proline isomerization within the PHD3-Bromo linker, thereby disrupting the PHD3-Bromo interface and facilitating binding of the MLL1-PHD3 domain to the CyP33-RRM domain. H3K4me3/2 and CyP33-RRM target different surfaces of MLL1-PHD3 and can bind simultaneously to form a ternary complex. Furthermore, the MLL1-CyP33 interaction is required for repression of HOXA9 and HOXC8 genes in vivo. Our results highlight the role of PHD3-Bromo cassette as a regulatory platform, orchestrating MLL1 binding of H3K4me3/2 marks and cyclophilin-mediated repression through HDAC recruitment.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21404360 C.G.Kalodimos (2011).
NMR reveals novel mechanisms of protein activity regulation.
  Protein Sci, 20, 773-782.  
21131971 P.Sarkar, T.Saleh, S.R.Tzeng, R.B.Birge, and C.G.Kalodimos (2011).
Structural basis for regulation of the Crk signaling protein by a proline switch.
  Nat Chem Biol, 7, 51-57.
PDB codes: 2l3p 2l3q 2l3s
20677349 N.McCarthy (2010).
Leukaemia: MLL makes friends and influences.
  Nat Rev Cancer, 10, 529.  
21164480 W.W.Tsai, Z.Wang, T.T.Yiu, K.C.Akdemir, W.Xia, S.Winter, C.Y.Tsai, X.Shi, D.Schwarzer, W.Plunkett, B.Aronow, O.Gozani, W.Fischle, M.C.Hung, D.J.Patel, and M.C.Barton (2010).
TRIM24 links a non-canonical histone signature to breast cancer.
  Nature, 468, 927-932.
PDB codes: 3o33 3o34 3o35 3o36 3o37
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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