The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system
The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system
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DOI：
10.1101/gad.12.9.1338
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发表时间：
1998-05-01
影响因子：
10.5
通讯作者：
Sauer, RT
中科院分区：
文献类型：
--
作者：
Gottesman, S;Roche, E;Sauer, RT
大肠杆菌中翻译的中断可能会导致在新生链中添加Ii残基羧基末端肽尾。这种修饰由SsrA RNA（也称为10Sa RNA和tmRNA）介导，并标记标记用于蛋白水解的标记多肽。在体内的λ阻遏物的氨基末端结构域的变异体轴承这个羧基末端SsrA肽标签的降解在这里显示依赖于细胞质蛋白酶ClpXP和ClpAP。SsrA标记的底物的体外降解用纯化的组分再现，并且需要具有野生型SsrA尾的底物、ClpP和ClpA或ClpX两者以及ATP的存在。Clp依赖性蛋白水解导致SsrA标记的氨基结构域底物在32 ℃下的大部分降解，但另外的蛋白酶有助于这些SsrA标记的底物中的一些在39 ℃下的降解。在SsrA质量控制监视中起作用的多种细胞质蛋白酶的存在表明，SsrA标签被设计成作为蛋白水解的相对混杂的信号。具有能够识别该标签的不同降解系统可以增加降解能力，允许降解各种不同的标记蛋白质，或允许SsrA标记的蛋白质在不同的生长条件下降解。
Interruption of translation in Escherichia coli can lead to the addition of an Ii-residue carboxy-terminal peptide tail to the nascent chain. This modification is mediated by SsrA RNA (also called 10Sa RNA and tmRNA) and marks the tagged polypeptide for proteolysis. Degradation in vivo of lambda repressor amino-terminal domain variants bearing this carboxy-terminal SsrA peptide tag is shown here to depend on the cytoplasmic proteases ClpXP and ClpAP. Degradation in vitro of SsrA-tagged substrates was reproduced with purified components and required a substrate with a wild-type SsrA tail, the presence of both ClpP and either ClpA or ClpX, and ATP. Clp-dependent proteolysis accounts for most degradation of SsrA-tagged amino-domain substrates at 32 degrees C, but additional proteases contribute to the degradation of some of these SsrA-tagged substrates at 39 degrees C. The existence of multiple cytoplasmic proteases that function in SsrA quality-control surveillance suggests that the SsrA tag is designed to serve as a relatively promiscuous signal for proteolysis. Having diverse degradation systems able to recognize this tag may increase degradation capacity, permit degradation of a wide variety of different tagged proteins, or allow SsrA-tagged proteins to be degraded under different growth conditions.