Tag Recycling in the Pup-Proteasome System is Essential for Mycobacterium smegmatis Survival Under Starvation Conditions,Molecular Microbiology

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Tag Recycling in the Pup-Proteasome System is Essential for Mycobacterium smegmatis Survival Under Starvation Conditions
Molecular Microbiology ( IF 2.6 ) Pub Date : 2024-09-05 , DOI: 10.1111/mmi.15312
Erez Zerbib ₁ , Roni Levin ₁ , Eyal Gur ₁

Affiliation

Many bacteria possess proteasomes and a tagging system that is functionally analogous to the ubiquitin system. In this system, Pup, the tagging protein, marks protein targets for proteasomal degradation. Despite the analogy to the ubiquitin system, where the ubiquitin tag is recycled, it remained unclear whether Pup is similarly recycled, given how the bacterial proteasome does not include a depupylase. We previously showed in vitro that as Pup lacks effective proteasome degradation sites, it is released from the proteasome following target degradation, remaining conjugated to a degradation fragment that can be later depupylated. Here, we tested this model in Mycobacterium smegmatis, using a Pup mutant that is effectively degraded by the proteasome. Our findings indicate that Pup recycling not only occurs in vivo but is also essential to maintain normal pupylome levels and to support bacterial survival under starvation conditions. Accordingly, Pup recycling is an essential process in the mycobacterial Pup-proteasome system.

中文翻译：

幼崽蛋白酶体系统中的标签回收对于耻垢分枝杆菌在饥饿条件下的生存至关重要

许多细菌具有蛋白酶体和标记系统，该系统在功能上类似于泛素系统。在该系统中，标记蛋白 Pup 标记蛋白酶体降解的蛋白质靶标。尽管类似于泛素系统，其中泛素标签被回收，但鉴于细菌蛋白酶体不包含脱脂蛋白酶，目前尚不清楚 Pup 是否被类似回收。我们之前在体外表明，由于 Pup 缺乏有效的蛋白酶体降解位点，它在靶标降解后从蛋白酶体中释放出来，与稍后可以去甲醛化的降解片段保持偶联。在这里，我们在耻垢分枝杆菌中测试了这个模型，使用了被蛋白酶体有效降解的 Pup 突变体。我们的研究结果表明，幼崽回收不仅发生在体内，而且对于维持正常的幼崽水平和支持细菌在饥饿条件下的存活也是必不可少的。因此，幼崽回收是分枝杆菌幼崽蛋白酶体系统中的一个重要过程。

更新日期：2024-09-05

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