The origins and evolution of ubiquitination sites
The origins and evolution of ubiquitination sites
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DOI：
10.1039/c2mb25052g
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Levy, Yaakov
中科院分区：
文献类型：
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作者：
Hagai, Tzachi;Toth-Petroczy, Agnes;Levy, Yaakov
蛋白质泛素化是真核生物中各种途径调控的核心。到目前为止，在数百种蛋白质中研究了泛素化的过程及其细胞结果。尽管如此，这一监管机制的演变尚未得到全面讨论。在这里，我们量化了泛素化和SUMO化（小泛素样调节剂）位点的进化变化率。我们估计了它们首次出现的时间，并将它们与乙酰化和磷酸化位点以及未修饰的残基进行比较。我们观察到，研究的各种修改网站表现出类似的速率。哺乳动物的泛素化位点比未修饰的赖氨酸残基更保守，并且在分析真正的泛素化位点时观察到更高程度的相对保守性。对于泛素化过度保守的有限水平，可以提出各种原因，包括位点位置的变化，替代位点的存在以及调节途径的变化。我们观察到，消失的网站可能会被补偿的赖氨酸残基的存在非常接近，这是显着的相比，未修饰的赖氨酸残基的进化模式，特别是在无序的区域。这强调了分析功能残基附近窗口的重要性，以及泛素化机制在某个区域中泛素化残基的能力。使用原核生物的泛素化蛋白质的直系同源物，我们研究了泛素化位点是如何形成的，并观察到，虽然有时序列添加和重排涉及，在许多情况下，泛素化机制利用一个已经存在的序列，而不显着改变it.Finally，我们研究了泛素化的进化，这是与其他修改，推断这些复杂的调控模块是如何演变的。我们的研究提供了初步的见解泛素化位点的形成，它们在不同物种中的保守程度，以及它们与其他翻译后修饰的共同进化。
Protein ubiquitination is central to the regulation of various pathways in eukaryotes. The process of ubiquitination and its cellular outcome were investigated in hundreds of proteins to date. Despite this, the evolution of this regulatory mechanism has not yet been addressed comprehensively. Here, we quantify the rates of evolutionary changes of ubiquitination and SUMOylation (Small Ubiquitin-like MOdifier) sites. We estimate the time at which they first appeared, and compare them to acetylation and phosphorylation sites and to unmodified residues. We observe that the various modification sites studied exhibit similar rates. Mammalian ubiquitination sites are weakly more conserved than unmodified lysine residues, and a higher degree of relative conservation is observed when analyzing bona fide ubiquitination sites. Various reasons can be proposed for the limited level of excess conservation of ubiquitination, including shifts in locations of the sites, the presence of alternative sites, and changes in the regulatory pathways. We observe that disappearance of sites may be compensated by the presence of a lysine residue in close proximity, which is significant when compared to evolutionary patterns of unmodified lysine residues, especially in disordered regions. This emphasizes the importance of analyzing a window in the vicinity of functional residues, as well as the capability of the ubiquitination machinery to ubiquitinate residues in a certain region. Using prokaryotic orthologs of ubiquitinated proteins, we study how ubiquitination sites were formed, and observe that while sometimes sequence additions and rearrangements are involved, in many cases the ubiquitination machinery utilizes an already existing sequence without significantly changing it. Finally, we examine the evolution of ubiquitination, which is linked with other modifications, to infer how these complex regulatory modules have evolved. Our study gives initial insights into the formation of ubiquitination sites, their degree of conservation in various species, and their co-evolution with other posttranslational modifications.