Characterization of the interaction between the tumour suppressor p53 and heme and its role in the protein conformational dynamics studied by various spectroscopic techniques and hydrogen/deuterium exchange coupled with mass spectrometry

0579255 - FZÚ 2024 RIV NL eng J - Journal Article
Vávra, J. - Sergunin, A. - Pompach, P. - Savchenko, Dariia - Hraníček, J. - Šloufová, I. - Shimizu, T. - Martinková, M.
Characterization of the interaction between the tumour suppressor p53 and heme and its role in the protein conformational dynamics studied by various spectroscopic techniques and hydrogen/deuterium exchange coupled with mass spectrometry.
Journal of Inorganic Biochemistry. Roč. 243, June (2023), č. článku 112180. ISSN 0162-0134. E-ISSN 1873-3344
R&D Projects: GA MŠMT(CZ) EF16_019/0000760
Grant - others:OP VVV - SOLID21(XE) CZ.02.1.01/0.0/0.0/16_019/0000760
Institutional support: RVO:68378271
Keywords : conformational dynamics * intrinsically disordered regions * Heme interaction * Heme-responsive sensor * p53 transcription factor * signal transduction
OECD category: Inorganic and nuclear chemistry
Impact factor: 3.9, year: 2022
Method of publishing: Limited access
https://doi.org/10.1016/j.jinorgbio.2023.112180

The tumour suppressor p53 regulates the expression of a myriad of proteins that are important for numerous cellular processes. Aside from DNA, p53 can interact with many types of partners including proteins and small organic molecules. In this study, we used various spectroscopic studies to conduct a thorough biophysical characterization of the interaction between p53 and heme concerning the oxidation, spin, coordination, and ligand state of heme iron. We found that the p53 oligomeric state and zinc biding ability are preserved upon the interaction with heme. Moreover, we described the effect of heme binding on the conformational dynamics of p53 by hydrogen/deuterium exchange coupled with mass spectrometry. Specifically, the conformational flexibility of p53 is significantly increased upon interaction with heme, while its affinity to a specific DNA sequence is reduced by heme. The inhibitory effect of DNA binding by heme is partially reversible.
Permanent Link: https://hdl.handle.net/11104/0348102