Evidence for allosteric effects on p53 oligomerization induced by phosphorylation
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F18%3A00077905" target="_blank" >RIV/00209805:_____/18:00077905 - isvavai.cz</a>
Alternative codes found
RIV/68081707:_____/18:00488457
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/pro.3344" target="_blank" >https://onlinelibrary.wiley.com/doi/abs/10.1002/pro.3344</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/pro.3344" target="_blank" >10.1002/pro.3344</a>
Alternative languages
Result language
angličtina
Original language name
Evidence for allosteric effects on p53 oligomerization induced by phosphorylation
Original language description
p53 is a tetrameric protein with a thermodynamically unstable deoxyribonucleic acid (DNA)-binding domain flanked by intrinsically disordered regulatory domains that control its activity. The unstable and disordered segments of p53 allow high flexibility as it interacts with binding partners and permits a rapid on/off switch to control its function. The p53 tetramer can exist in multiple conformational states, any of which can be stabilized by a particular modification. Here, we apply the allostery model to p53 to ask whether evidence can be found that the "activating" C-terminal phosphorylation of p53 stabilizes a specific conformation of the protein in the absence of DNA. We take advantage of monoclonal antibodies for p53 that measure indirectly the following conformations: unfolded, folded, and tetrameric. A double antibody capture enzyme linkedimmunosorbent assay was used to observe evidence of conformational changes of human p53 upon phosphorylation by casein kinase 2 in vitro. It was demonstrated that oligomerization and stabilization of p53 wild-type conformation results in differential exposure of conformational epitopes PAb1620, PAb240, and DO12 that indicates a reduction in the "unfolded" conformation and increases in the folded conformation coincide with increases in its oligomerization state. These data highlight that the oligomeric conformation of p53 can be stabilized by an activating enzyme and further highlight the utility of the allostery model when applied to understanding the regulation of unstable and intrinsically disordered proteins.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GBP206%2F12%2FG151" target="_blank" >GBP206/12/G151: Center of novel approaches to bioanalysis and molecular diagnostics</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Protein science
ISSN
0961-8368
e-ISSN
—
Volume of the periodical
27
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
523-530
UT code for WoS article
000422956600015
EID of the result in the Scopus database
2-s2.0-85040837464