Interaction of the p53 DNA-Binding Domain with Its N-Terminal Extension Modulates the Stability of the p53 Tetramer
2011

How p53's Structure Affects Its Function

publication 10 minutes Evidence: moderate

Author Information

Author(s): Natan Eviatar, Baloglu Cetin, Pagel Kevin, Freund Stefan M.V., Morgner Nina, Robinson Carol V., Fersht Alan R., Joerger Andreas C.

Primary Institution: MRC Laboratory of Molecular Biology

Hypothesis

The N-terminal extension of p53 modulates the stability and function of its DNA-binding domain.

Conclusion

The study reveals that the N-terminal extension of p53 enhances the stability of its DNA-binding domain and affects its aggregation properties.

Supporting Evidence

  • NMR and X-ray crystallography revealed that Trp91 interacts with Arg174 in the DNA-binding domain.
  • The presence of the N-terminal extension increases the melting temperature of the DNA-binding domain.
  • The study shows that constructs lacking the N-terminal extension are more prone to aggregation.

Takeaway

This study shows that a small part of the p53 protein helps it stay stable and work properly, which is important for preventing cancer.

Methodology

The study used NMR and X-ray crystallography to investigate the interactions between the N-terminal extension and the DNA-binding domain of p53.

Limitations

The study primarily focuses on specific constructs of p53, which may not fully represent the behavior of the full-length protein in all contexts.

Digital Object Identifier (DOI)

10.1016/j.jmb.2011.03.047

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