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PDBsum entry 5e24
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Transport/DNA binding/DNA
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PDB id
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5e24
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Contents |
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370 a.a.
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38 a.a.
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424 a.a.
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References listed in PDB file
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Key reference
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Title
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Structure and function of the su(h)-Hairless repressor complex, The major antagonist of notch signaling in drosophila melanogaster.
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Authors
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Z.Yuan,
H.Praxenthaler,
N.Tabaja,
R.Torella,
A.Preiss,
D.Maier,
R.A.Kovall.
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Ref.
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Plos Biol, 2016,
14,
e1002509.
[DOI no: ]
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PubMed id
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Abstract
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Notch is a conserved signaling pathway that specifies cell fates in metazoans.
Receptor-ligand interactions induce changes in gene expression, which is
regulated by the transcription factor CBF1/Su(H)/Lag-1 (CSL). CSL interacts with
coregulators to repress and activate transcription from Notch target genes.
While the molecular details of the activator complex are relatively well
understood, the structure-function of CSL-mediated repressor complexes is poorly
defined. In Drosophila, the antagonist Hairless directly binds Su(H) (the fly
CSL ortholog) to repress transcription from Notch targets. Here, we determine
the X-ray structure of the Su(H)-Hairless complex bound to DNA. Hairless binding
produces a large conformational change in Su(H) by interacting with residues in
the hydrophobic core of Su(H), illustrating the structural plasticity of CSL
molecules to interact with different binding partners. Based on the structure,
we designed mutants in Hairless and Su(H) that affect binding, but do not affect
formation of the activator complex. These mutants were validated in vitro by
isothermal titration calorimetry and yeast two- and three-hybrid assays.
Moreover, these mutants allowed us to solely characterize the repressor function
of Su(H) in vivo.
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