小柯机器人

宿主通过泛素化脂多糖来抵御细菌感染
2021-05-21 20:22

英国剑桥大学MRC分子生物学实验室Felix Randow、Elsje G. Otten等研究人员合作发现,细菌感染过程中RNF213介导脂多糖的泛素化。2021年5月19日,国际知名学术期刊《自然》在线发表了这一成果。

研究人员发现,入侵胞质的沙门氏菌上的泛素外层是通过非蛋白底物(细菌脂多糖LPS的脂质A部分)的泛素化,并由E3泛素连接酶环指蛋白213(RNF213)形成的。RNF213是烟雾病(moyamoya disease)的危险因素,这是导致中风的上颈样颈内动脉进行性狭窄(特别是在儿童中)。 RNF213限制了胞质沙门氏菌的增殖,对于直接(通过LPS的泛素化)和间接(通过招募LUBAC,这是一种下游E3连接酶,可添加M1连接的泛素链的到已经存在的泛素外层)产生的细菌泛素外壳都是必不可少。

在缺少RNF213的细胞中,细菌不会吸引泛素依赖性自噬受体或诱导抗菌自噬。入侵胞质的沙门氏菌上LPS的泛素化需要RNF213的动力蛋白样核心,而不是其RING结构域。因此,LPS的泛素化依赖于E3外壳中的RZ指。总而言之,这项研究表明,泛素化作用不仅仅局限于蛋白质底物,以及LPS的泛素化作用会触发细胞自主免疫,并且研究人员推测,除LPS以外的非蛋白质物质也可能会被泛素化。

据介绍,泛素化是真核生物中广泛的翻译后蛋白质修饰,并且能够标记侵入细胞质的细菌,进行抗菌自噬。细菌上泛素化底物的身份尚不清楚。

附:英文原文

Title: Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection

Author: Elsje G. Otten, Emma Werner, Ana Crespillo-Casado, Keith B. Boyle, Vimisha Dharamdasani, Claudio Pathe, Balaji Santhanam, Felix Randow

Issue&Volume: 2021-05-19

Abstract: Ubiquitylation is a widespread post-translational protein modification in eukaryotes and marks bacteria that invade the cytosol as cargo for antibacterial autophagy1,2,3. The identity of the ubiquitylated substrate on bacteria is unknown. Here we show that the ubiquitin coat on Salmonella that invade the cytosol is formed through the ubiquitylation of a non-proteinaceous substrate, the lipid A moiety of bacterial lipopolysaccharide (LPS), by the E3 ubiquitin ligase ring finger protein 213 (RNF213). RNF213 is a risk factor for moyamoya disease4,5, which is a progressive stenosis of the supraclinoid internal carotid artery that causes stroke (especially in children)6,7. RNF213 restricts the proliferation of cytosolic Salmonella and is essential for the generation of the bacterial ubiquitin coat, both directly (through the ubiquitylation of LPS) and indirectly (through the recruitment of LUBAC, which is a downstream E3 ligase that adds M1-linked ubiquitin chains onto pre-existing ubiquitin coats8). In cells that lack RNF213, bacteria do not attract ubiquitin-dependent autophagy receptors or induce antibacterial autophagy. The ubiquitylation of LPS on Salmonella that invade the cytosol requires the dynein-like core of RNF213, but not its RING domain. Instead, ubiquitylation of LPS relies on an RZ finger in the E3 shell. We conclude that ubiquitylation extends beyond protein substrates and that ubiquitylation of LPS triggers cell-autonomous immunity, and we postulate that non-proteinaceous substances other than LPS may also become ubiquitylated.

DOI: 10.1038/s41586-021-03566-4

Source: https://www.nature.com/articles/s41586-021-03566-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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