Stability of p53 homologs.
Most proteins have not evolved for maximal thermal stability. Some are only marginally stable, as for example, the DNA-binding domains of p53 and its homologs, whose kinetic and thermodynamic stabilities are strongly correlated. Here, we applied high-throughput methods using a real-time PCR thermocy...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3480436?pdf=render |
| _version_ | 1818509114492321792 |
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| author | Tobias Brandt Joel L Kaar Alan R Fersht Dmitry B Veprintsev |
| author_facet | Tobias Brandt Joel L Kaar Alan R Fersht Dmitry B Veprintsev |
| author_sort | Tobias Brandt |
| collection | DOAJ |
| description | Most proteins have not evolved for maximal thermal stability. Some are only marginally stable, as for example, the DNA-binding domains of p53 and its homologs, whose kinetic and thermodynamic stabilities are strongly correlated. Here, we applied high-throughput methods using a real-time PCR thermocycler to study the stability of several full-length orthologs and paralogs of the p53 family of transcription factors, which have diverse functions, ranging from tumour suppression to control of developmental processes. From isothermal denaturation fluorimetry and differential scanning fluorimetry, we found that full-length proteins showed the same correlation between kinetic and thermodynamic stability as their isolated DNA-binding domains. The stabilities of the full-length p53 orthologs were marginal and correlated with the temperature of their organism, paralleling the stability of the isolated DNA-binding domains. Additionally, the paralogs p63 and p73 were significantly more stable and long-lived than p53. The short half-life of p53 orthologs and the greater persistence of the paralogs may be biologically relevant. |
| first_indexed | 2024-12-10T22:41:02Z |
| format | Article |
| id | doaj.art-106edf49e9e24e7ea443bfe3b492e26a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T22:41:02Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-106edf49e9e24e7ea443bfe3b492e26a2022-12-22T01:30:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4788910.1371/journal.pone.0047889Stability of p53 homologs.Tobias BrandtJoel L KaarAlan R FershtDmitry B VeprintsevMost proteins have not evolved for maximal thermal stability. Some are only marginally stable, as for example, the DNA-binding domains of p53 and its homologs, whose kinetic and thermodynamic stabilities are strongly correlated. Here, we applied high-throughput methods using a real-time PCR thermocycler to study the stability of several full-length orthologs and paralogs of the p53 family of transcription factors, which have diverse functions, ranging from tumour suppression to control of developmental processes. From isothermal denaturation fluorimetry and differential scanning fluorimetry, we found that full-length proteins showed the same correlation between kinetic and thermodynamic stability as their isolated DNA-binding domains. The stabilities of the full-length p53 orthologs were marginal and correlated with the temperature of their organism, paralleling the stability of the isolated DNA-binding domains. Additionally, the paralogs p63 and p73 were significantly more stable and long-lived than p53. The short half-life of p53 orthologs and the greater persistence of the paralogs may be biologically relevant.http://europepmc.org/articles/PMC3480436?pdf=render |
| spellingShingle | Tobias Brandt Joel L Kaar Alan R Fersht Dmitry B Veprintsev Stability of p53 homologs. PLoS ONE |
| title | Stability of p53 homologs. |
| title_full | Stability of p53 homologs. |
| title_fullStr | Stability of p53 homologs. |
| title_full_unstemmed | Stability of p53 homologs. |
| title_short | Stability of p53 homologs. |
| title_sort | stability of p53 homologs |
| url | http://europepmc.org/articles/PMC3480436?pdf=render |
| work_keys_str_mv | AT tobiasbrandt stabilityofp53homologs AT joellkaar stabilityofp53homologs AT alanrfersht stabilityofp53homologs AT dmitrybveprintsev stabilityofp53homologs |