How do cancer-related mutations affect the oligomerisation state of the p53 tetramerisation domain?
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- dc.contributor.author Nicolini, Federica
- dc.contributor.author Todorovski, Toni
- dc.contributor.author Puig, Eduard
- dc.contributor.author Díaz-Lobo, Mireia
- dc.contributor.author Vilaseca, Marta
- dc.contributor.author García, Jesús
- dc.contributor.author Andreu Martínez, David
- dc.contributor.author Giralt, Ernest
- dc.date.accessioned 2023-10-02T06:47:18Z
- dc.date.available 2023-10-02T06:47:18Z
- dc.date.issued 2023
- dc.description.abstract Tumour suppressor p53 plays a key role in the development of cancer and has therefore been widely studied in recent decades. While it is well known that p53 is biologically active as a tetramer, the tetramerisation mechanism is still not completely understood. p53 is mutated in nearly 50% of cancers, and mutations can alter the oligomeric state of the protein, having an impact on the biological function of the protein and on cell fate decisions. Here, we describe the effects of a number of representative cancer-related mutations on tetramerisation domain (TD) oligomerisation defining a peptide length that permits having a folded and structured domain, thus avoiding the effect of the flanking regions and the net charges at the N- and C-terminus. These peptides have been studied under different experimental conditions. We have applied a variety of techniques, including circular dichroism (CD), native mass spectrometry (MS) and high-field solution NMR. Native MS allows us to detect the native state of complexes maintaining the peptide complexes intact in the gas phase; the secondary and quaternary structures were analysed in solution by NMR, and the oligomeric forms were assigned by diffusion NMR experiments. A significant destabilising effect and a variable monomer population were observed for all the mutants studied.
- dc.description.sponsorship This research was funded by MINECO-FEDER (BIO 2016-75327-R).
- dc.format.mimetype application/pdf
- dc.identifier.citation Nicolini F, Todorovski T, Puig E, Díaz-Lobo M, Vilaseca M, García J, Andreu D, Giralt E. How do cancer-related mutations affect the oligomerisation state of the p53 tetramerisation domain? Curr Issues Mol Biol. 2023 Jun 7;45(6):4985-5004. DOI: 10.3390/cimb45060317
- dc.identifier.doi http://dx.doi.org/10.3390/cimb45060317
- dc.identifier.issn 1467-3037
- dc.identifier.uri http://hdl.handle.net/10230/58015
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof Curr Issues Mol Biol. 2023 Jun 7;45(6):4985-5004
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2016-75327-R
- dc.rights © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Cancer mutations
- dc.subject.keyword Diffusion NMR
- dc.subject.keyword High-field NMR
- dc.subject.keyword Native MS
- dc.subject.keyword p53
- dc.subject.keyword p53 dimer
- dc.subject.keyword p53 tetramer
- dc.subject.keyword p53 tetramerisation domain
- dc.title How do cancer-related mutations affect the oligomerisation state of the p53 tetramerisation domain?
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion