3LQH

Crystal structure of MLL1 PHD3-Bromo in the free form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression.

Wang, Z.Song, J.Milne, T.A.Wang, G.G.Li, H.Allis, C.D.Patel, D.J.

(2010) Cell 141: 1183-1194

  • DOI: https://doi.org/10.1016/j.cell.2010.05.016
  • Primary Citation of Related Structures:  
    2KU7, 3LPY, 3LQH, 3LQI, 3LQJ

  • PubMed 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.


  • Organizational Affiliation

    Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histone-lysine N-methyltransferase MLL183Homo sapiensMutation(s): 0 
Gene Names: MLLALL1CXXC7HRXHTRXKMT2AMLL1TRX1
EC: 2.1.1.43
UniProt & NIH Common Fund Data Resources
Find proteins for Q03164 (Homo sapiens)
Explore Q03164 
Go to UniProtKB:  Q03164
PHAROS:  Q03164
GTEx:  ENSG00000118058 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ03164
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.219α = 90
b = 71.879β = 90
c = 93.867γ = 90
Software Package:
Software NamePurpose
MAR345dtbdata collection
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-07-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-07-26
    Changes: Refinement description, Source and taxonomy
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations