Specific recognition of p53 tetramers by peptides derived from p53 interacting proteins.
Specific recognition of p53 tetramers by peptides derived from p53 interacting proteins.
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DOI：
10.1371/journal.pone.0038060
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Friedler A
中科院分区：
文献类型：
--
作者：
Gabizon R;Brandt T;Sukenik S;Lahav N;Lebendiker M;Shalev DE;Veprintsev D;Friedler A
寡聚在调节许多蛋白质的活性和调节它们之间的相互作用方面起着重要作用。P53是一种同源四聚体转录因子，在肿瘤抑制中起着关键作用。它的四聚结构域包含在其C-末端结构域中，C-末端结构域是许多蛋白质-蛋白质相互作用的位点。这些都可以依赖或调节P53的寡聚化。在这里，我们筛选了一系列来自已知与四聚体P53 C末端结构域(P53CTD)结合的蛋白质的多肽，并鉴定了10个结合肽。我们用荧光各向异性定量表征了它们与p53CTD的结合。这些多肽以微摩尔亲和力结合四聚体p53CTD。尽管结合多肽的电荷很高，但静电对相互作用的贡献很小。核磁共振研究表明，这些多肽与p53CTD结合在特定的位置。在圆二色热变性研究中，与p53四聚结构域直接结合的多肽WS100B(81-92)和稳定p53CTD的PKCα(281-295)出现了最显著的化学位移偏差。使用分析超速离心法，我们发现几个多肽优先与P53四聚体结合。我们的结果表明，P53的蛋白质-蛋白质相互作用依赖于P53的寡聚化状态。我们认为，多肽可能被用来调节P53的寡聚化。
Oligomerization plays a major role in regulating the activity of many proteins, and in modulating their interactions. p53 is a homotetrameric transcription factor that has a pivotal role in tumor suppression. Its tetramerization domain is contained within its C-terminal domain, which is a site for numerous protein-protein interactions. Those can either depend on or regulate p53 oligomerization. Here we screened an array of peptides derived from proteins known to bind the tetrameric p53 C-terminal domain (p53CTD) and identified ten binding peptides. We quantitatively characterized their binding to p53CTD using fluorescence anisotropy. The peptides bound tetrameric p53CTD with micromolar affinities. Despite the high charge of the binding peptides, electrostatics contributed only mildly to the interactions. NMR studies indicated that the peptides bound p53CTD at defined sites. The most significant chemical shift deviations were observed for the peptides WS100B(81–92), which bound directly to the p53 tetramerization domain, and PKCα(281–295), which stabilized p53CTD in circular dichroism thermal denaturation studies. Using analytical ultracentrifugation, we found that several of the peptides bound preferentially to p53 tetramers. Our results indicate that the protein-protein interactions of p53 are dependent on the oligomerization state of p53. We conclude that peptides may be used to regulate the oligomerization of p53.
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影响因子：
3.5
作者：
Hayouka, Zvi;Hurevich, Mattan;Friedler, Assaf
通讯作者：
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DOI：
10.1016/j.bbrc.2010.02.100
发表时间：
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期刊：
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通讯作者：
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DOI：
10.1016/j.str.2009.11.011
发表时间：
2010-02-10
期刊：
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影响因子：
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通讯作者：
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DOI：
10.1073/pnas.0501459102
发表时间：
2005-03-29
影响因子：
11.1
作者：
Fernandez-Fernandez, MR;Veprintsev, DB;Fersht, AR
通讯作者：
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