Oxidative protein folding: many different ways to introduce disulfide bonds.
Oxidative protein folding: many different ways to introduce disulfide bonds.
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氧化蛋白质折叠：引入二硫键的多种不同方法。
DOI：
10.1089/ars.2006.8.731
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发表时间：
2006
影响因子：
6.6
通讯作者：
Kadokura,Hiroshi
中科院分区：
文献类型：
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作者：
Kadokura,Hiroshi
732 KADOKURA外膜孔的存在，允许小分子扩散出细胞（13）。多年来，人们一直认为结构二硫键形成的催化作用发生在细菌外质和真核内质网中。然而，近年来进行的研究表明，许多其他隔间也具有二硫键形成的催化系统。在革兰氏阳性细菌枯草芽孢杆菌中，仅鉴定出极少数具有二硫键的胞质外蛋白（11）。尽管如此，最近的研究表明，这种生物也进化出了二硫键形成的催化系统。Möller和Hederstedt总结了在这种细菌的细胞表面发现的硫醇二硫氧化还原酶的信息。有趣的是，在枯草芽孢杆菌中，所有的酶都附着在质膜的胞质外一侧，而大肠杆菌是水溶性的（11）。这可能反映了这样一个事实，即枯草芽孢杆菌缺乏外膜，而在大肠杆菌中，外膜可以阻止蛋白质从细胞包膜扩散。正如Koehler等人所讨论的，线粒体（IMS）的膜间空间含有许多具有二硫键的蛋白质(7)。Mesecke等人最近的研究发现，IMS中存在由Mia40p和Erv1p组成的二硫中继系统（7,9）。就像DsbA和PDI对新易位的还原蛋白所做的那样（5,10），氧化的Mia40p通过形成混合二硫络合物与新导入的还原蛋白结合。随后的复合体的分解允许输入的蛋白质在IMS中折叠。还原后的Mia40p被Erv1p再循环回到氧化后的活性形式，Erv1p可以将电子传递给O2。不考虑二硫继电器系统之间的相似之处，差异也存在。例如，Erv1p的耗尽或降低Mia40p的条件阻碍了底物的输入，导致Mia40p-Erv1p系统将底物的氧化折叠与它们进入IMS的耦合模型(9)。另一方面，DsbA-DsbB或Pdi1p-Ero1p系统在蛋白质易位过程中的参与尚不清楚。此外，Mia40p缺乏CXXC活性位点基序，这是二硫键形成酶DsbA和Pdi1p的标志。此外，Mia40p鉴定的底物是所谓的小Tim蛋白和Cox17p，它们具有半胱氨酸的保守模式（双CX3C基序或双CX9C基序），Mia40p被认为在其中引入了二硫键（7,9）。在DsbA或Pdi1p底物中没有观察到这种特殊的半胱氨酸残基排列。观察Mia40p是否可以在没有这些基序的情况下将二硫键引入蛋白质将是一件有趣的事情。应该提到的是，正如Koehler等人和Mesecke等人所指出的（7,9），考虑到线粒体IMS与细菌外质的进化关系，IMS中存在许多二硫键结合蛋白和二硫键形成机制本身可能并不那么令人惊讶。
732 KADOKURA presence of the outer-membrane pores that allow the diffusion of small molecules out of the cell (13). For years it had been assumed that catalysis of structural disulfide bond formation takes place in the bacterial periplasm and eukaryotic ER. However, studies carried out in recent years revealed that many other compartments also have catalytic systems for disulfide bond formation. In the gram-positive bacterium, Bacillus subtilis, only a very few extracytoplasmic proteins with disulfide bonds have been identified (11). Nonetheless, recent works established that this organism also has evolved catalytic systems for disulfide bond formation. Möller and Hederstedt summarize the information on the thiol–disulfide oxidoreductase found on the cell surface of this bacterium. Interestingly, in B. subtilis, all of the enzymes are tethered to the extracytoplasmic side of the plasma membrane, in contrast to E. coli DsbA which is water soluble (11). This may reflect the fact that B. subtilis lacks an outer membrane which, in E. coli, prevents the diffusion of proteins from the cell envelope. As Koehler et al. discuss, the intermembrane space of mitochondria (IMS) harbors a number of proteins that have disulfide bonds (7). Recent findings by Mesecke et al. showed that there is a disulfide relay system in the IMS comprised of Mia40p and Erv1p (7, 9). Like DsbA and PDI do for newly translocated reduced protein (5, 10), oxidized Mia40p binds newly imported reduced proteins via the formation of a mixed disulfide complex. The subsequent resolution of the complex allows the imported protein to be folded in the IMS. The reduced Mia40p is then recycled back to its oxidized active form by Erv1p that can pass electrons to O2. Regardless of the parallels seen among the disulfide relay systems, differences also exist. For example, depletion of Erv1p or conditions reducing Mia40p blocked the import of the substrates, leading to the model that the Mia40p-Erv1p system couples the oxidative folding of the substrates to their import into the IMS (9). On the other hand, the involvement of the DsbA–DsbB or Pdi1p–Ero1p system in the protein translocation process is not known. In addition, Mia40p lacks a CXXC active site motif, a hallmark of the disulfide bondforming enzymes DsbA and Pdi1p. Moreover, the substrates of Mia40p identified are so called small Tim proteins and Cox17p that have a conserved pattern of cysteines (a twin CX3C motif or twin CX9C motif), into which Mia40p is thought to introduce disulfide bonds (7, 9). Such specific arrangement of cysteine residues is not observed for the substrates of DsbA or Pdi1p. It will be interesting to see whether Mia40p can introduce disulfide bonds into proteins without these motifs.It should be mentioned that, as Koehler et al. and Mesecke et al. noted (7, 9), the existence in the IMS of many disulfide bonded proteins and the machinery for disulfide bond formation itself may not be so surprising given the evolutionary relationship of the mitochondrial IMS to the bacterial periplasm.
影响因子：
6.6
作者：
Gon, Stephanie;Faulkner, Melinda J.;Beckwith, Jon
通讯作者：
Beckwith, Jon
DsbB 胞质环在泛醌-DsbB 复合物催化周转中的作用
DOI：
--
发表时间：
2006
期刊：
Antioxidants ＆ Redox Signaling 8・5-6
影响因子：
--
作者：
高橋洋平;稲葉謙次;伊藤維昭
通讯作者：
伊藤維昭