2YPA: Structure Of The Scl:e47:lmo2:ldb1 Complex Bound To Dna

Citation:
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.
PDB ID: 2YPADownload
MMDB ID: 112157
PDB Deposition Date: 2012/10/30
Updated in MMDB: 2013/08
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2YPA: hexameric; determined by author and by software (PISA)
Molecular Components in 2YPA
Label Count Molecule
Proteins (4 molecules)
1
T-cell Acute Lymphocytic Leukemia Protein 1(Gene symbol: TAL1)
Molecule annotation
1
Transcription Factor E2-alpha(Gene symbol: TCF3)
Molecule annotation
1
Rhombotin-2(Gene symbol: LMO2)
Molecule annotation
1
LIM Domain-binding Protein 1(Gene symbol: LDB1)
Molecule annotation
Nucleotides(2 molecules)
1
Ebox Forward
Molecule annotation
1
Ebox Reverse
Molecule annotation
Chemicals (4 molecules)
1
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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