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PDBsum entry 4xai
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Transcription
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PDB id
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4xai
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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 corepressor assembly by the orphan nuclear receptor tlx.
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Authors
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X.Zhi,
X.E.Zhou,
Y.He,
K.Searose-Xu,
C.L.Zhang,
C.C.Tsai,
K.Melcher,
H.E.Xu.
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Ref.
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Genes Dev, 2015,
29,
440-450.
[DOI no: ]
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PubMed id
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Abstract
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The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the
adult brain and functions primarily as a transcription repressor through
recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide
motif termed the Atro box. Here we report crystal structures of the human and
insect TLX ligand-binding domain in complex with Atro box peptides. In these
structures, TLX adopts an autorepressed conformation in which its helix H12
occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed
conformation forms a novel binding pocket with residues from helix H3 that
accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro
box. Mutations that weaken the TLX-Atrophin interaction compromise the
repressive activity of TLX, demonstrating that this interaction is required for
Atrophin to confer repressor activity to TLX. Moreover, the autorepressed
conformation is conserved in the repressor class of orphan nuclear receptors,
and mutations of corresponding residues in other members of this class of
receptors diminish their repressor activities. Together, our results establish
the functional conservation of the autorepressed conformation and define a key
sequence motif in the Atro box that is essential for TLX-mediated repression.
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