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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Crystal structure of a multidomain human p53 tetramer bound to the natural CDKN1A (p21) p53-response element

Soheila Emamzadah1, Laurence Tropia, Thanos D Halazonetis

  • 1Department of Molecular Biology, University of Geneva, Geneva, Switzerland.

Molecular Cancer Research : MCR
|September 22, 2011
PubMed

Insights

The p53 tumor suppressor protein

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Genetics

Background:

  • The p53 protein is a crucial tumor suppressor.
  • p53 acts as a sequence-specific DNA-binding transcription factor.
  • Previous structures lacked p53 bound to natural response elements.

Purpose of the Study:

  • To determine the structure of human p53 bound to a natural response element.
  • To elucidate the mechanism of p53 DNA binding to the CDKN1A (p21) gene promoter.
  • To compare DNA binding to natural vs. artificial DNA sites.

Main Methods:

  • X-ray crystallography
  • Protein-DNA complex structural determination
  • Homotetramer complex analysis

Main Results:

  • The structure of a human p53 homotetramer bound to the natural CDKN1A (p21) response element was determined.
  • p53 DNA binding involves an induced fit mechanism.
  • Conformational changes in loop L1 are more pronounced with the natural element than previously observed.

Conclusions:

  • The structure provides insights into p53's recognition of specific DNA sequences.
  • The findings support a model where DNA binding induces significant conformational changes in p53's DNA-binding domain.
  • Loop L1 conformation in the natural complex may represent a more advanced state of induced fit.

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