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PDBsum entry 2ypb
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Immune system
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PDB id
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2ypb
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References listed in PDB file
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Key reference
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Title
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Structural basis for lmo2-Driven recruitment of the scl:e47bhlh heterodimer to hematopoietic-Specific transcriptional targets.
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Authors
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K.El omari,
S.J.Hoosdally,
K.Tuladhar,
D.Karia,
E.Hall-Ponselé,
O.Platonova,
P.Vyas,
R.Patient,
C.Porcher,
E.J.Mancini.
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Ref.
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Cell Rep, 2013,
4,
135-147.
[DOI no: ]
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PubMed id
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Abstract
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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.
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