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Wild-type p53 adopts a 'mutant'-like conformation when bound to DNA
T D Halazonetis1, L J Davis, A N Kandil
1Department of Cancer Research, Merck Research Laboratories, West Point, PA 19486.
The EMBO Journal
|March 1, 1993
Summary
Wild-type p53 protein changes conformation upon DNA binding, adopting a mutant-like structure. This conformational change may regulate the DNA binding activity and function of wild-type p53.
Area of Science:
- Molecular Biology
- Cancer Research
- Protein Conformation
Background:
- p53 acts as a negative regulator of cell growth.
- Mutant p53 proteins are prevalent in human tumors and exhibit distinct immunoreactivity compared to wild-type p53.
- Wild-type p53 possesses sequence-specific DNA binding activity.
Purpose of the Study:
- To investigate the conformational changes of wild-type p53 upon DNA binding.
- To explore the potential regulatory mechanism of wild-type p53 function through conformational alterations.
Main Methods:
- Utilized conformation-specific monoclonal antibodies (e.g., PAb421, PAb1620, PAb246) to distinguish between wild-type and mutant p53.
- Demonstrated changes in wild-type p53 conformation at both N- and C-termini upon DNA interaction.
Main Results:
- Wild-type p53 undergoes a significant conformational change when binding to DNA.
- This induced conformation resembles that of 'mutant'-like p53.
- Such long-range conformational changes upon DNA binding are rare among DNA-binding proteins.
Conclusions:
- Wild-type p53's DNA binding activity and overall function may be modulated by its ability to adopt distinct conformations.
- This conformational plasticity offers a novel regulatory mechanism for p53 function in cellular processes.