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PDBsum entry 3co7
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Transcription/DNA
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PDB id
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3co7
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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 DNA recognition by foxo1 and its regulation by posttranslational modification.
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Authors
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M.M.Brent,
R.Anand,
R.Marmorstein.
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Ref.
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Structure, 2008,
16,
1407-1416.
[DOI no: ]
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PubMed id
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Abstract
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FoxO transcription factors regulate the transcription of genes that control
metabolism, cellular proliferation, stress tolerance, and possibly life span. A
number of posttranslational modifications within the forkhead DNA-binding domain
regulate FoxO-mediated transcription. We describe the crystal structures of
FoxO1 bound to three different DNA elements and measure the change in FoxO1-DNA
affinity with acetylation and phosphorylation. The structures reveal additional
contacts and increased DNA distortion for the highest affinity DNA site. The
flexible wing 2 region of the forkhead domain was not observed in the structures
but is necessary for DNA binding, and we show that p300 acetylation in wing 2
reduces DNA affinity. We also show that MST1 phosphorylation of FoxO1 prevents
high-affinity DNA binding. The observation that FoxO-DNA affinity varies between
response elements and with posttranslational modifications suggests that
modulation of FoxO-DNA affinity is an important component of FoxO regulation in
health and misregulation in disease.
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Figure 3.
Figure 3. Schematic Showing FoxO1 DBD Interactions with IRE
and DBE1 DNA Sequences
(A and B) Differences in hydrogen
bonding between the DBE and IRE sequences are highlighted in
green. Bases that are contacted directly or through
water-mediated interactions are shaded. Phosphates that are
contacted directly or through water-mediated interactions are
highlighted in red.
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Figure 4.
Figure 4. Binding of FoxO1 DBD and Truncation Mutants to
Cognate DNA Sites
(A–D) EMSA binding studies to IRE and
DBE2 DNA using C-terminally truncated FoxO1 DBD constructs.
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Structure
(2008,
16,
1407-1416)
copyright 2008.
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