ElaD, a Deubiquitinating protease expressed by E. coli.

ElaD, a Deubiquitinating protease expressed by E. coli.
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DOI:
10.1371/journal.pone.0000381
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发表时间:
2007-04-18
期刊:
影响因子:
3.7
通讯作者:
Ploegh HL
Ploegh HL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Catic A;Misaghi S;Korbel GA;Ploegh HL

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泛素和泛素样蛋白(Ubl)被设计用于修饰真核生物中的多肽。泛素或Ubls与底物蛋白的共价结合可以通过特异性水解酶逆转。靶向泛素和Ubls的一组特定的半胱氨酸蛋白酶CE家族在真核生物、原核生物和病毒中具有同源物。我们克隆并分析了E.大肠杆菌蛋白elaD,其与特异于SUMO和Nedd 8的ULP/SENP蛋白酶家族的真核CE家族成员远亲。elaD以前被误认为是一种假定的硫酸酯酶/磷酸酶,在体外是一种有效和特异的去泛素化酶。有趣的是,elaD存在于所有肠道致病性E.大肠杆菌菌株,但明显缺乏肠外致病性菌株(ExPEC)。这种蛋白酶的其他同系物可以在阿米巴多噬菌拟态病毒和α-、β-和γ-变形菌中找到。因此,ULP/SENP相关水解酶在细菌中的表达延伸到植物病原体和大肠杆菌、嗜肺军团菌、立克次体、衣原体和沙门氏菌的医学相关菌株,其中elaD直系同源物sseL最近被鉴定为具有去泛素化活性的毒力因子。作为一个对比,我们的系统发育和功能的检查表明,古老的真核ULP/SENP蛋白酶也有潜力的泛素特异性水解,这表明这个肽酶家族的早期共同起源。
Ubiquitin and ubiquitin-like proteins (Ubl) are designed to modify polypeptides in eukaryotes. Covalent binding of ubiquitin or Ubls to substrate proteins can be reversed by specific hydrolases. One particular set of cysteine proteases, the CE clan, which targets ubiquitin and Ubls, has homologs in eukaryotes, prokaryotes, and viruses. We have cloned and analyzed the E. coli protein elaD, which is distantly related to eukaryotic CE clan members of the ULP/SENP protease family that are specific for SUMO and Nedd8. Previously misannotated as a putative sulfatase/phosphatase, elaD is an efficient and specific deubiquitinating enzyme in vitro. Interestingly, elaD is present in all intestinal pathogenic E. coli strains, but conspicuously absent from extraintestinal pathogenic strains (ExPECs). Further homologs of this protease can be found in Acanthamoeba Polyphaga Mimivirus, and in Alpha-, Beta-and Gammaproteobacteria. The expression of ULP/SENP-related hydrolases in bacteria therefore extends to plant pathogens and medically relevant strains of Escherichia coli, Legionella pneumophila, Rickettsiae, Chlamydiae, and Salmonellae, in which the elaD ortholog sseL has recently been identified as a virulence factor with deubiquitinating activity. As a counterpoint, our phylogenetic and functional examination reveals that ancient eukaryotic ULP/SENP proteases also have the potential of ubiquitin-specific hydrolysis, suggesting an early common origin of this peptidase clan.
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发表时间: 2007-01
期刊: PLOS PATHOGENS
影响因子: 6.7
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