Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity.
Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity.
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DOI：
10.1038/s41467-021-26061-w
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发表时间：
2021-10-01
影响因子：
16.6
通讯作者：
Impens F
中科院分区：
文献类型：
--
作者：
Thery F;Martina L;Asselman C;Zhang Y;Vessely M;Repo H;Sedeyn K;Moschonas GD;Bredow C;Teo QW;Zhang J;Leandro K;Eggermont D;De Sutter D;Boucher K;Hochepied T;Festjens N;Callewaert N;Saelens X;Dermaut B;Knobeloch KP;Beling A;Sanyal S;Radoshevich L;Eyckerman S;Impens F
ISG15是一种干扰素刺激的泛素样蛋白，可与底物蛋白结合(ISG化)以对抗微生物感染，但其潜在机制仍不清楚。在这里，我们使用类似病毒的颗粒捕获技术来鉴定ISG15结合蛋白，并发现Ring inger Protein 213(RNF213)是ISG15相互作用蛋白和ISGylated蛋白的细胞传感器。RNF213是一种特性不佳的干扰素诱导的巨蛋白，在烟雾病(一种罕见的脑血管疾病)中经常发生突变。我们报道了干扰素诱导RNF213在脂滴上的ISG化和寡聚化，在那里它作为ISGylated蛋白质的传感器。我们发现RNF213在体外和体内都具有广泛的抗菌活性，可以对抗单核细胞增生性李斯特菌、单纯疱疹病毒1型、人类呼吸道合胞病毒和柯萨奇病毒B3的感染，并观察到RNF213与细胞内细菌的显著共定位。综上所述，我们的发现为ISG化途径提供了分子见解，并揭示了RNF213是一个关键的抗菌效应器。在微生物感染期间，蛋白质被泛素样蛋白ISG15修饰。在这里，作者发现RNF213是脂滴表面ISGylated蛋白质的传感器，表明RNF213具有抗病毒特性，但也直接针对受感染细胞中的细胞内细菌。
ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we use a virus-like particle trapping technology to identify ISG15-binding proteins and discover Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We report that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We show that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection with Listeria monocytogenes, herpes simplex virus 1, human respiratory syncytial virus and coxsackievirus B3, and we observe a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector. During microbial infection, proteins are modified by the ubiquitin-like protein ISG15. Here, the authors uncover RNF213 as a sensor for ISGylated proteins on the surface of lipid droplets, showing that RNF213 has antiviral properties but also directly targets intracellular bacteria in infected cells.
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影响因子：
16.6
作者：
Arumughan, Anup;Roske, Yvette;Barth, Carolin;Forero, Laura Lleras;Bravo-Rodriguez, Kenny;Redel, Alexandra;Kostova, Simona;McShane, Erik;Opitz, Robert;Faelber, Katja;Rau, Kirstin;Mielke, Thorsten;Daumke, Oliver;Selbach, Matthias;Sanchez-Garcia, Elsa;Rocks, Oliver;Panakova, Daniela;Heinemann, Udo;Wanker, Erich E.
通讯作者：
Wanker, Erich E.
影响因子：
16.6
作者：
Eyckerman S;Titeca K;Van Quickelberghe E;Cloots E;Verhee A;Samyn N;De Ceuninck L;Timmerman E;De Sutter D;Lievens S;Van Calenbergh S;Gevaert K;Tavernier J
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Tavernier J
影响因子：
32.4
作者：
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通讯作者：
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影响因子：
11.4
作者：
Du, Yang;Duan, Tianhao;Wang, Rong-Fu
通讯作者：
Wang, Rong-Fu
影响因子：
3.7
作者：
BAZZIGHER, L;PAVLOVIC, J;STAEHELI, P
通讯作者：
STAEHELI, P