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.
Conformational dynamics
Heme interaction
Heme-responsive sensor
Intrinsically disordered regions
Signal transduction
p53 transcription factor
Journal
Journal of inorganic biochemistry
ISSN: 1873-3344
Titre abrégé: J Inorg Biochem
Pays: United States
ID NLM: 7905788
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
17
12
2022
revised:
04
03
2023
accepted:
06
03
2023
medline:
11
4
2023
pubmed:
20
3
2023
entrez:
19
3
2023
Statut:
ppublish
Résumé
The tumour suppressor p53 regulates the expression of a myriad of proteins that are important for numerous cellular processes, including apoptosis, cell cycle arrest, DNA repair, metabolism, and even autophagy and ferroptosis. Aside from DNA, p53 can interact with many types of partners including proteins and small organic molecules. The ability of p53 to interact with heme has been reported so far. 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. We discuss the potential heme binding sites in p53 with respect to the observed conformational dynamics changes and perturbed DNA-binding ability of p53 upon interaction with heme.
Identifiants
pubmed: 36934467
pii: S0162-0134(23)00062-4
doi: 10.1016/j.jinorgbio.2023.112180
pii:
doi:
Substances chimiques
Hydrogen
7YNJ3PO35Z
Deuterium
AR09D82C7G
Heme
42VZT0U6YR
Tumor Suppressor Protein p53
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112180Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jakub Vavra reports financial support was provided by Charles University. Dariya Savchenko reports financial support was provided by Ministry of Education Youth and Sports of the Czech Republic. Marketa Martinkova reports financial support was provided by Ministry of Education Youth and Sports of the Czech Republic. Petr Pompach reports financial support was provided by Ministry of Education Youth and Sports of the Czech Republic.