Stability of p53 Homologs
Stability of p53 Homologs
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DOI：
10.1371/journal.pone.0047889
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发表时间：
2012-10-24
期刊：
影响因子：
3.7
通讯作者：
Veprintsev, Dmitry B.
中科院分区：
文献类型：
--
作者：
Brandt, Tobias;Kaar, Joel L.;Veprintsev, Dmitry B.
大多数蛋白质并没有进化到达到最大的热稳定性。有些只是略微稳定，例如，p53的dna结合结构域及其同源物，其动力学和热力学稳定性是密切相关的。在这里，我们采用高通量方法，使用实时PCR热循环仪来研究p53家族转录因子的几个全长同源物和类似物的稳定性，这些转录因子具有不同的功能，从肿瘤抑制到发育过程的控制。通过等温变性荧光法和差示扫描荧光法，我们发现全长蛋白的动力学和热力学稳定性与其分离的dna结合域具有相同的相关性。全长p53同源物的稳定性是边缘的，并且与其生物体的温度相关，与分离的dna结合结构域的稳定性相似。此外，p63和p73明显比p53更稳定，寿命更长。p53同源基因较短的半衰期和相似基因较强的持久性可能与生物学有关。
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.