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PDBsum entry 3m9e
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Transcription/DNA
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PDB id
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3m9e
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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 of a thyroid hormone receptor DNA-Binding domain homodimer bound to an inverted palindrome DNA response element.
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Authors
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Y.Chen,
M.A.Young.
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Ref.
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Mol Endocrinol, 2010,
24,
1650-1664.
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PubMed id
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Abstract
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Thyroid hormone receptor (TR), as a member of the nuclear hormone receptor
family, can recognize and bind different classes of DNA response element targets
as either a monomer, a homooligomer, or a heterooligomer. We report here the
first crystal structure of a homodimer TR DNA-binding domain (DBD) in complex
with an inverted repeat class of thyroid response element (TRE). The structure
shows a nearly symmetric structure of the TR DBD assembled on the F2 TRE where
the base recognition contacts in the homodimer DNA complex are conserved
relative to the previously published structure of a TR-9-cis-retinoic acid
receptor heterodimer DNA complex. The new structure also reveals that the T-box
region of the DBD can function as a structural hinge that enables a large degree
of flexibility in the position of the C-terminal extension helix that connects
the DBD to the ligand-binding domain. Although the isolated TR DBDs exist as
monomers in solution, we have measured highly cooperative binding of the two TR
DBD subunits onto the inverted repeat DNA sequence. This suggests that elements
of the DBD can influence the specific TR oligomerization at target genes, and it
is not just interactions between the ligand-binding domains that are responsible
for TR oligomerization at target genes. Mutational analysis shows that
intersubunit contacts at the DBD C terminus account for some, but not all, of
the cooperative homodimer TR binding to the inverted repeat class TRE.
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