Prokaryotic ubiquitin-like protein (Pup) proteome of Mycobacterium tuberculosis [corrected] .
Prokaryotic ubiquitin-like protein (Pup) proteome of Mycobacterium tuberculosis [corrected] .
复制标题
结核分枝杆菌的核酸泛素样蛋白（PUP）蛋白质组[校正]。
DOI：
10.1371/journal.pone.0008589
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发表时间：
2010-01-06
期刊：
影响因子：
3.7
通讯作者：
Darwin KH
中科院分区：
文献类型：
--
作者：
Festa RA;McAllister F;Pearce MJ;Mintseris J;Burns KE;Gygi SP;Darwin KH
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）中的前泛素样蛋白（Propylactic ubiquitin-like protein，Pup）是原核生物中第一个已知的翻译后小蛋白修饰物，并且以类似于真核生物中泛素（ubiquitin，Ub）介导的蛋白质水解的方式靶向几种蛋白质以被细菌蛋白酶体降解。为了确定Mtb中的pupylation程度，我们使用串联亲和纯化来鉴定其“pupylome”。质谱鉴定了604个纯化蛋白质中的55个，其具有确认的pupylation位点。四十四种蛋白质，包括那些与和没有确定的pupylation网站，进行了测试，作为底物的蛋白水解结核分枝杆菌。在稳态条件下，大多数测试蛋白质没有在降解突变体中积累，这表明并非所有的蛋白质化靶标都必须是稳态条件下蛋白酶体的底物。四种蛋白质参与结核分枝杆菌的发病机制，Icl（异柠檬酸裂解酶），Ino 1（肌醇-1-磷酸合酶），MtrA（结核分枝杆菌反应调节剂A）和PhoP（磷酸盐反应调节剂P），在降解缺陷型结核分枝杆菌中显示出改变的水平。Icl、Ino 1和MtrA在Mtb降解突变体中积累，表明这些蛋白质靶向蛋白酶体。出乎意料的是，PhoP存在于野生型Mtb中，但在降解突变体中检测不到。综上所述，这些数据表明，pupylation调节Mtb中的许多蛋白质，并不总是导致降解。
Prokaryotic ubiquitin-like protein (Pup) in Mycobacterium tuberculosis (Mtb) is the first known post-translational small protein modifier in prokaryotes, and targets several proteins for degradation by a bacterial proteasome in a manner akin to ubiquitin (Ub) mediated proteolysis in eukaryotes. To determine the extent of pupylation in Mtb, we used tandem affinity purification to identify its “pupylome”. Mass spectrometry identified 55 out of 604 purified proteins with confirmed pupylation sites. Forty-four proteins, including those with and without identified pupylation sites, were tested as substrates of proteolysis in Mtb. Under steady state conditions, the majority of the test proteins did not accumulate in degradation mutants, suggesting not all targets of pupylation are necessarily substrates of the proteasome under steady state conditions. Four proteins implicated in Mtb pathogenesis, Icl (isocitrate lyase), Ino1 (inositol-1-phosphate synthase), MtrA (Mtb response regulator A) and PhoP (phosphate response regulator P), showed altered levels in degradation defective Mtb. Icl, Ino1 and MtrA accumulated in Mtb degradation mutants, suggesting these proteins are targeted to the proteasome. Unexpectedly, PhoP was present in wild type Mtb but undetectable in the degradation mutants. Taken together, these data demonstrate that pupylation regulates numerous proteins in Mtb and may not always lead to degradation.
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