2YPA

Structure of the SCL:E47:LMO2:LDB1 complex bound to DNA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.226 

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Literature

Structural Basis for Lmo2-Driven Recruitment of the Scl:E47bHLH Heterodimer to Hematopoietic-Specific Transcriptional Targets.

El Omari, K.Hoosdally, S.J.Tuladhar, K.Karia, D.Hall-Ponsele, E.Platonova, O.Vyas, P.Patient, R.Porcher, C.Mancini, E.J.

(2013) Cell Rep 4: 135

  • DOI: https://doi.org/10.1016/j.celrep.2013.06.008
  • Primary Citation of Related Structures:  
    2YPA, 2YPB

  • PubMed Abstract: 

    Cell fate is governed by combinatorial actions of transcriptional regulators assembling into multiprotein complexes. However, the molecular details of how these complexes form are poorly understood. One such complex, which contains the basic-helix-loop-helix heterodimer SCL:E47 and bridging proteins LMO2:LDB1, critically regulates hematopoiesis and induces T cell leukemia. Here, we report the crystal structure of (SCL:E47)bHLH:LMO2:LDB1LID bound to DNA, providing a molecular account of the network of interactions assembling this complex. This reveals an unexpected role for LMO2. Upon binding to SCL, LMO2 induces new hydrogen bonds in SCL:E47, thereby strengthening heterodimer formation. This imposes a rotation movement onto E47 that weakens the heterodimer:DNA interaction, shifting the main DNA-binding activity onto additional protein partners. Along with biochemical analyses, this illustrates, at an atomic level, how hematopoietic-specific SCL sequesters ubiquitous E47 and associated cofactors and supports SCL's reported DNA-binding-independent functions. Importantly, this work will drive the design of small molecules inhibiting leukemogenic processes.


  • Organizational Affiliation

    Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
T-CELL ACUTE LYMPHOCYTIC LEUKEMIA PROTEIN 191Homo sapiensMutation(s): 0 
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Find proteins for P17542 (Homo sapiens)
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Go to UniProtKB:  P17542
PHAROS:  P17542
GTEx:  ENSG00000162367 
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UniProt GroupP17542
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
TRANSCRIPTION FACTOR E2-ALPHA82Homo sapiensMutation(s): 0 
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Find proteins for P15923 (Homo sapiens)
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PHAROS:  P15923
GTEx:  ENSG00000071564 
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UniProt GroupP15923
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
RHOMBOTIN-2145Homo sapiensMutation(s): 0 
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Find proteins for P25791 (Homo sapiens)
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PHAROS:  P25791
GTEx:  ENSG00000135363 
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UniProt GroupP25791
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
LIM DOMAIN-BINDING PROTEIN 151Homo sapiensMutation(s): 0 
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Find proteins for Q86U70 (Homo sapiens)
Explore Q86U70 
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PHAROS:  Q86U70
GTEx:  ENSG00000198728 
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UniProt GroupQ86U70
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Entity ID: 5
MoleculeChains LengthOrganismImage
EBOX FORWARD11Homo sapiens
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Entity ID: 6
MoleculeChains LengthOrganismImage
EBOX REVERSE11Homo sapiens
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.226 
  • Space Group: F 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 102.966α = 90
b = 141.044β = 90
c = 148.793γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHENIXphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-07-31
    Type: Initial release