Structural evolution of C-terminal domains in the p53 family
Structural evolution of C-terminal domains in the p53 family
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DOI：
10.1038/sj.emboj.7601764
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发表时间：
2007-07-25
期刊：
影响因子：
11.4
通讯作者：
Doetsch, Volker
中科院分区：
文献类型：
--
作者：
Ou, Horng Der;Loehr, Frank;Doetsch, Volker
P53、P63和P73的四聚体状态被认为是该蛋白家族的标志之一。虽然DNA结合域(DBD)在脊椎动物和无脊椎动物中高度保守，但从C端到DBD的序列却高度分化。特别是，模式生物秀丽线虫和果蝇的P53形式的寡聚域(OD)不能通过序列分析来鉴定。在这里，我们介绍了它们的ODs的溶液结构，并表明它们彼此之间以及与人类P53显著不同。CEP-1含有一个OD结构域和一个无菌α基序(SAM)结构域，形成二聚体而不是四聚体。Dmp53结构的特征是额外的N-末端β-链和C-末端螺旋。两个结构域的截断分析表明，附加的结构元件是稳定OD结构所必需的，这为SAM结构域提供了新的功能。此外，这些结构显示了一条潜在的进化路径，从祖先的二聚体形式到四聚体形式，带有额外的稳定元件，到哺乳动物P53的四聚化域。
The tetrameric state of p53, p63, and p73 has been considered one of the hallmarks of this protein family. While the DNA binding domain (DBD) is highly conserved among vertebrates and invertebrates, sequences C-terminal to the DBD are highly divergent. In particular, the oligomerization domain ( OD) of the p53 forms of the model organisms Caenorhabditis elegans and Drosophila cannot be identified by sequence analysis. Here, we present the solution structures of their ODs and show that they both differ significantly from each other as well as from human p53. CEP-1 contains a composite domain of an OD and a sterile alpha motif (SAM) domain, and forms dimers instead of tetramers. The Dmp53 structure is characterized by an additional N-terminal beta-strand and a C-terminal helix. Truncation analysis in both domains reveals that the additional structural elements are necessary to stabilize the structure of the OD, suggesting a new function for the SAM domain. Furthermore, these structures show a potential path of evolution from an ancestral dimeric form over a tetrameric form, with additional stabilization elements, to the tetramerization domain of mammalian p53.