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Bacterial rhomboid proteases mediate quality control of orphan membrane proteins.
The EMBO Journal ( IF 11.4 ) Pub Date : 2020-04-27 , DOI: 10.15252/embj.2019102922
Guangyu Liu 1 , Stephen E Beaton 2 , Adam G Grieve 1 , Rhiannon Evans 2 , Miranda Rogers 1 , Kvido Strisovsky 3 , Fraser A Armstrong 2 , Matthew Freeman 1 , Rachel M Exley 1 , Christoph M Tang 1
Affiliation  

Although multiprotein membrane complexes play crucial roles in bacterial physiology and virulence, the mechanisms governing their quality control remain incompletely understood. In particular, it is not known how unincorporated, orphan components of protein complexes are recognised and eliminated from membranes. Rhomboids, the most widespread and largest superfamily of intramembrane proteases, are known to play key roles in eukaryotes. In contrast, the function of prokaryotic rhomboids has remained enigmatic. Here, we show that the Shigella sonnei rhomboid proteases GlpG and the newly identified Rhom7 are involved in membrane protein quality control by specifically targeting components of respiratory complexes, with the metastable transmembrane domains (TMDs) of rhomboid substrates protected when they are incorporated into a functional complex. Initial cleavage by GlpG or Rhom7 allows subsequent degradation of the orphan substrate. Given the occurrence of this strategy in an evolutionary ancient organism and the presence of rhomboids in all domains of life, it is likely that this form of quality control also mediates critical events in eukaryotes and protects cells from the damaging effects of orphan proteins.

中文翻译:

细菌菱形蛋白酶介导孤儿膜蛋白的质量控制。

尽管多蛋白膜复合物在细菌生理学和毒力中起着至关重要的作用,但控制其质量控制的机制仍不完全清楚。特别是,尚不清楚蛋白质复合物的未掺入的孤儿成分是如何从膜中识别和消除的。菱形是最广泛和最大的膜内蛋白酶超家族,已知在真核生物中起关键作用。相比之下,原核菱形体的功能仍然是个谜。在这里,我们表明,Shigella sonnei 菱形蛋白酶 GlpG 和新发现的 Rhom7 通过特异性靶向呼吸复合物的成分参与膜蛋白质量控制,菱形底物的亚稳态跨膜结构域 (TMD) 在它们被整合到功能性药物中时受到保护。复杂的。GlpG 或 Rhom7 的初始切割允许随后的孤儿底物降解。鉴于这种策略在进化的古代生物中的出现以及在生命的所有领域都存在菱形,这种形式的质量控制很可能也介导真核生物中的关键事件并保护细胞免受孤儿蛋白的破坏性影响。
更新日期:2020-04-27
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