Multiple domains of bacterial and human Lon proteases define substrate selectivity.
Multiple domains of bacterial and human Lon proteases define substrate selectivity.
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细菌和人类 Lon 蛋白酶的多个结构域定义了底物选择性
DOI：
10.1038/s41426-018-0148-4
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发表时间：
2018-08-17
影响因子：
13.2
通讯作者：
Zhang JR
中科院分区：
文献类型：
--
作者：
He L;Luo D;Yang F;Li C;Zhang X;Deng H;Zhang JR
在许多原核和真核生物中，Lon蛋白酶选择性地降解异常蛋白或某些正常蛋白，以响应环境和细胞条件。然而，正常蛋白的底物选择背后的机制在很大程度上仍然未知。在这项研究中，我们鉴定了10个新的底物ofF。在我们之前的研究中，共从21个候选底物中发现了tularensisLon，这是单一研究中发现的数量最多的新型Lon底物。这些和其他已知的Lon底物的跨物种降解表明，人类的Lon不能降解许多细菌的Lon底物，这提示了天然Lon变体的“生物体适应”底物选择机制。然而，单独用细菌的Lon替代人类Lon的N、A和P结构域并不能使人类蛋白酶降解相同的细菌Lon底物。这一结果表明，“生物体适应”底物选择取决于多个结构域的Lon蛋白酶。进一步的体外蛋白水解和质谱分析揭示了细菌和人类Lon变体之间相似的底物裂解模式，这是在底物的P（−1）位点上主要代表亮氨酸、丙氨酸和其他疏水氨基酸的例证。这些观察结果表明，Lon蛋白酶至少在一定程度上是通过与同一生物体中的蛋白质进行精细结构匹配来选择底物的。
The Lon protease selectively degrades abnormal proteins or certain normal proteins in response to environmental and cellular conditions in many prokaryotic and eukaryotic organisms. However, the mechanism(s) behind the substrate selection of normal proteins remains largely unknown. In this study, we identified 10 new substrates ofF. tularensisLon from a total of 21 candidate substrates identified in our previous work, the largest number of novel Lon substrates from a single study. Cross-species degradation of these and other known Lon substrates revealed that human Lon is unable to degrade many bacterial Lon substrates, suggestive of a “organism-adapted” substrate selection mechanism for the natural Lon variants. However, individually replacing the N, A, and P domains of human Lon with the counterparts of bacterial Lon did not enable the human protease to degrade the same bacterial Lon substrates. This result showed that the “organism-adapted” substrate selection depends on multiple domains of the Lon proteases. Further in vitro proteolysis and mass spectrometry analysis revealed a similar substrate cleavage pattern between the bacterial and human Lon variants, which was exemplified by predominant representation of leucine, alanine, and other hydrophobic amino acids at the P(−1) site within the substrates. These observations suggest that the Lon proteases select their substrates at least in part by fine structural matching with the proteins in the same organisms.
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DOI：
10.1128/genomea.00135-12
发表时间：
2013-01
期刊：
Genome announcements
影响因子：
--
作者：
Antwerpen MH;Schacht E;Kaysser P;Splettstoesser WD
通讯作者：
Splettstoesser WD
土拉弗朗西斯菌 LVS 的蛋白酶位点是哺乳动物宿主的应激耐受和感染所必需的
影响因子：
3.1
作者：
He, Lihong;Nair, Manoj Kumar Mohan;Zhang, Jing-Ren
通讯作者：
Zhang, Jing-Ren
影响因子：
10.5
作者：
Gur, Eyal;Sauer, Robert T.
通讯作者：
Sauer, Robert T.
影响因子：
14.8
作者：
Greenfield, Norma J.
通讯作者：
Greenfield, Norma J.
影响因子：
2.8
作者：
Grall, Nathalie;Livny, Jonathan;Meibom, Karin L.
通讯作者：
Meibom, Karin L.