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PDBsum entry 5mcu
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Transcription
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PDB id
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5mcu
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References listed in PDB file
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Key reference
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Title
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New insights into the role of DNA shape on its recognition by p53 proteins.
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Authors
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D.Golovenko,
B.Bräuning,
P.Vyas,
T.E.Haran,
H.Rozenberg,
Z.Shakked.
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Ref.
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Structure, 2018,
26,
1237.
[DOI no: ]
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PubMed id
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Abstract
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The tumor suppressor p53 acts as a transcription factor recognizing diverse DNA
response elements (REs). Previous structural studies of p53-DNA complexes
revealed non-canonical Hoogsteen geometry of A/T base pairs at conserved CATG
motifs leading to changes in DNA shape and its interface with p53. To study the
effects of DNA shape on binding characteristics, we designed REs with modified
base pairs "locked" into either Hoogsteen or Watson-Crick form. Here
we present crystal structures of these complexes and their thermodynamic and
kinetic parameters, demonstrating that complexes with Hoogsteen base pairs are
stabilized relative to those with all-Watson-Crick base pairs. CATG motifs are
abundant in p53REs such as GADD45 and p53R2 related to cell-cycle arrest and DNA
repair. The high-resolution structures of these complexes validate their
propensity to adopt the unique Hoogsteen-induced structure, thus providing
insights into the functional role of DNA shape and broadening the mechanisms
that contribute to DNA recognition by proteins.
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