• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

细菌去泛素化酶和泛素 E3 连接酶之间的相互作用调节军团菌吞噬体上的泛素动态。

Interplay between bacterial deubiquitinase and ubiquitin E3 ligase regulates ubiquitin dynamics on Legionella phagosomes.

机构信息

Department of Respiratory Medicine and Center of Infection and Immunity, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital, Jilin University, Changchun, China.

The Key Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, China.

出版信息

Elife. 2020 Nov 2;9:e58114. doi: 10.7554/eLife.58114.

DOI:10.7554/eLife.58114
PMID:33136002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7669269/
Abstract

extensively modulates the host ubiquitin network to create the Legionella-containing vacuole (LCV) for its replication. Many of its virulence factors function as ubiquitin ligases or deubiquitinases (DUBs). Here, we identify Lem27 as a DUB that displays a preference for diubiquitin formed by K6, K11, or K48. Lem27 is associated with the LCV where it regulates Rab10 ubiquitination in concert with SidC and SdcA, two bacterial E3 ubiquitin ligases. Structural analysis of the complex formed by an active fragment of Lem27 and the substrate-based suicide inhibitor ubiquitin-propargylamide (PA) reveals that it harbors a fold resembling those in the OTU1 DUB subfamily with a Cys-His catalytic dyad and that it recognizes ubiquitin via extensive hydrogen bonding at six contact sites. Our results establish Lem27 as a DUB that functions to regulate protein ubiquitination on phagosomes by counteracting the activity of bacterial ubiquitin E3 ligases.

摘要

广泛调节宿主泛素网络，为军团菌复制创造含有军团菌的空泡 (LCV)。其许多毒力因子作为泛素连接酶或去泛素化酶 (DUB) 发挥作用。在这里，我们鉴定 Lem27 为一种 DUB，它对由 K6、K11 或 K48 形成的二泛素表现出偏好。Lem27 与 LCV 相关，在那里它与 SidC 和 SdcA 一起调节 Rab10 的泛素化，SidC 和 SdcA 是两种细菌 E3 泛素连接酶。由 Lem27 的活性片段和基于底物的自杀抑制剂泛素-炔丙酰胺 (PA) 形成的复合物的结构分析表明，它具有类似于 OTU1 DUB 亚家族的折叠，具有 Cys-His 催化二联体，并且通过六个接触位点的广泛氢键识别泛素。我们的结果确立 Lem27 为一种 DUB，通过拮抗细菌泛素 E3 连接酶的活性，在吞噬体上调节蛋白质泛素化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/c19348b83fba/elife-58114-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/4341e1b87e3a/elife-58114-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/d48455368ac9/elife-58114-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/33e3fcf4bb15/elife-58114-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/3c079db49351/elife-58114-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/5524816a9492/elife-58114-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/4a43bc5103ca/elife-58114-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/904812c09d0c/elife-58114-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/145db164d0ef/elife-58114-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/b56545b6636f/elife-58114-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/2474039bb36e/elife-58114-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/f4648c6d9e65/elife-58114-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/3212bbb820b0/elife-58114-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/294bc233a05b/elife-58114-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/c19348b83fba/elife-58114-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/4341e1b87e3a/elife-58114-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/d48455368ac9/elife-58114-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/33e3fcf4bb15/elife-58114-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/3c079db49351/elife-58114-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/5524816a9492/elife-58114-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/4a43bc5103ca/elife-58114-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/904812c09d0c/elife-58114-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/145db164d0ef/elife-58114-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/b56545b6636f/elife-58114-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/2474039bb36e/elife-58114-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/f4648c6d9e65/elife-58114-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/3212bbb820b0/elife-58114-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/294bc233a05b/elife-58114-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a332/7669269/c19348b83fba/elife-58114-resp-fig1.jpg

相似文献

1
Interplay between bacterial deubiquitinase and ubiquitin E3 ligase regulates ubiquitin dynamics on Legionella phagosomes.细菌去泛素化酶和泛素 E3 连接酶之间的相互作用调节军团菌吞噬体上的泛素动态。
Elife. 2020 Nov 2;9:e58114. doi: 10.7554/eLife.58114.
2
Bacterial ubiquitin ligases hijack the host deubiquitinase OTUB1 to inhibit MTORC1 signaling and promote autophagy.细菌泛素连接酶劫持宿主去泛素化酶 OTUB1 以抑制 MTORC1 信号传导并促进自噬。
Autophagy. 2024 Sep;20(9):1968-1983. doi: 10.1080/15548627.2024.2353492. Epub 2024 May 31.
3
The bacterial deubiquitinase Ceg23 regulates the association of Lys-63-linked polyubiquitin molecules on the phagosome.细菌去泛素化酶 Ceg23 调节吞噬体上 Lys-63 连接的多泛素分子的结合。
J Biol Chem. 2020 Feb 7;295(6):1646-1657. doi: 10.1074/jbc.RA119.011758. Epub 2020 Jan 6.
4
Structural Basis of Ubiquitin Recognition by a Bacterial Ovarian Tumor Deubiquitinase LotA.细菌性卵巢肿瘤去泛素化酶 LotA 识别泛素的结构基础。
J Bacteriol. 2022 Jan 18;204(1):e0037621. doi: 10.1128/JB.00376-21. Epub 2021 Oct 11.
5
The Legionella effector SidC defines a unique family of ubiquitin ligases important for bacterial phagosomal remodeling.军团菌效应蛋白 SidC 定义了一个独特的泛素连接酶家族，对细菌吞噬体重塑很重要。
Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10538-43. doi: 10.1073/pnas.1402605111. Epub 2014 Jul 8.
6
Legionella effectors SidC/SdcA ubiquitinate multiple small GTPases and SNARE proteins to promote phagosomal maturation.军团菌效应蛋白 SidC/SdcA 泛素化多种小 GTPases 和 SNARE 蛋白，以促进吞噬体成熟。
Cell Mol Life Sci. 2024 Jun 5;81(1):249. doi: 10.1007/s00018-024-05271-7.
7
Purification and functional characterization of the DUB domain of SdeA.SdeA的去泛素化酶结构域的纯化及功能表征
Methods Enzymol. 2019;618:343-355. doi: 10.1016/bs.mie.2018.12.024. Epub 2019 Feb 1.
8
Multi-tiered actions of effectors to modulate host Rab10 dynamics.效应物的多层次作用来调节宿主 Rab10 的动力学。
Elife. 2024 May 21;12:RP89002. doi: 10.7554/eLife.89002.
9
Ubiquitin Chains Modified by the Bacterial Ligase SdeA Are Protected from Deubiquitinase Hydrolysis.由细菌连接酶SdeA修饰的泛素链可免受去泛素化酶水解。
Biochemistry. 2017 Sep 12;56(36):4762-4766. doi: 10.1021/acs.biochem.7b00664. Epub 2017 Aug 18.
10
Structure of the Legionella Virulence Factor, SidC Reveals a Unique PI(4)P-Specific Binding Domain Essential for Its Targeting to the Bacterial Phagosome.嗜肺军团菌毒力因子SidC的结构揭示了一个独特的PI(4)P特异性结合结构域，该结构域对其靶向细菌吞噬体至关重要。
PLoS Pathog. 2015 Jun 12;11(6):e1004965. doi: 10.1371/journal.ppat.1004965. eCollection 2015 Jun.

引用本文的文献

1
IrsA, a novel, iron-regulated exoprotein that facilitates growth in low-iron conditions and modulates biofilm formation.IrsA是一种新型的铁调节外蛋白，它在低铁条件下促进生长并调节生物膜形成。
Microbiol Spectr. 2025 Jan 7;13(1):e0231324. doi: 10.1128/spectrum.02313-24. Epub 2024 Nov 29.
2
Structural insight into the distinct regulatory mechanism of the HEPN-MNT toxin-antitoxin system in Legionella pneumophila.解析 Legionella pneumophila 中 HEPN-MNT 毒素-抗毒素系统的独特调控机制的结构见解。
Nat Commun. 2024 Nov 24;15(1):10188. doi: 10.1038/s41467-024-54551-0.
3
Phosphoribosyl modification of poly-ubiquitin chains at the Legionella-containing vacuole prohibiting autophagy adaptor recognition.

本文引用的文献

1
Divergence of Legionella Effectors Reversing Conventional and Unconventional Ubiquitination.嗜肺军团菌效应蛋白在逆转传统和非传统泛素化方面的差异
Front Cell Infect Microbiol. 2020 Aug 21;10:448. doi: 10.3389/fcimb.2020.00448. eCollection 2020.
2
Phosphoinositides and the Fate of in Phagocytes.磷酸肌醇和吞噬细胞中 的命运。
Front Immunol. 2020 Jan 30;11:25. doi: 10.3389/fimmu.2020.00025. eCollection 2020.
3
The bacterial deubiquitinase Ceg23 regulates the association of Lys-63-linked polyubiquitin molecules on the phagosome.
磷核糖基化修饰含军团菌液泡中的多泛素链，阻止自噬衔接蛋白的识别。
Nat Commun. 2024 Aug 30;15(1):7481. doi: 10.1038/s41467-024-51273-1.
4
Sde proteins coordinate ubiquitin utilization and phosphoribosylation to establish and maintain the Legionella replication vacuole.Sde 蛋白协调泛素利用和磷酸核糖基化作用，以建立和维持军团菌复制空泡。
Nat Commun. 2024 Aug 30;15(1):7479. doi: 10.1038/s41467-024-51272-2.
5
Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms.军团菌通过具有独特催化机制的效应物来维持宿主细胞的泛素稳态。
Nat Commun. 2024 Jul 15;15(1):5953. doi: 10.1038/s41467-024-50311-2.
6
Legionella effectors SidC/SdcA ubiquitinate multiple small GTPases and SNARE proteins to promote phagosomal maturation.军团菌效应蛋白 SidC/SdcA 泛素化多种小 GTPases 和 SNARE 蛋白，以促进吞噬体成熟。
Cell Mol Life Sci. 2024 Jun 5;81(1):249. doi: 10.1007/s00018-024-05271-7.
7
Bactericidal effectors of the type IV secretion system: functional definition of the nuclease TfdA and structural determination of TfcB.IV型分泌系统的杀菌效应蛋白：核酸酶TfdA的功能定义及TfcB的结构测定
mBio. 2024 Jul 17;15(7):e0119824. doi: 10.1128/mbio.01198-24. Epub 2024 Jun 4.
8
Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms.嗜肺军团菌通过具有独特催化机制的效应蛋白维持宿主细胞泛素稳态。
Res Sq. 2024 May 20:rs.3.rs-4431542. doi: 10.21203/rs.3.rs-4431542/v1.
9
Bacterial ubiquitin ligases hijack the host deubiquitinase OTUB1 to inhibit MTORC1 signaling and promote autophagy.细菌泛素连接酶劫持宿主去泛素化酶 OTUB1 以抑制 MTORC1 信号传导并促进自噬。
Autophagy. 2024 Sep;20(9):1968-1983. doi: 10.1080/15548627.2024.2353492. Epub 2024 May 31.
10
Multi-tiered actions of effectors to modulate host Rab10 dynamics.效应物的多层次作用来调节宿主 Rab10 的动力学。
Elife. 2024 May 21;12:RP89002. doi: 10.7554/eLife.89002.
细菌去泛素化酶 Ceg23 调节吞噬体上 Lys-63 连接的多泛素分子的结合。
J Biol Chem. 2020 Feb 7;295(6):1646-1657. doi: 10.1074/jbc.RA119.011758. Epub 2020 Jan 6.
4
Legionella pneumophila regulates the activity of UBE2N by deamidase-mediated deubiquitination.嗜肺军团菌通过脱氨酶介导的去泛素化调节 UBE2N 的活性。
EMBO J. 2020 Feb 17;39(4):e102806. doi: 10.15252/embj.2019102806. Epub 2019 Dec 11.
5
Regulation of Phosphoribosyl-Linked Serine Ubiquitination by Deubiquitinases DupA and DupB.通过去泛素化酶 DupA 和 DupB 调节磷酸核糖基连接丝氨酸泛素化。
Mol Cell. 2020 Jan 2;77(1):164-179.e6. doi: 10.1016/j.molcel.2019.10.019. Epub 2019 Nov 12.
6
Deubiquitination of phosphoribosyl-ubiquitin conjugates by phosphodiesterase-domain-containing effectors.磷酸二酯酶结构域包含效应物对磷酸核糖基-泛素缀合物的去泛素化作用。
Proc Natl Acad Sci U S A. 2019 Nov 19;116(47):23518-23526. doi: 10.1073/pnas.1916287116. Epub 2019 Nov 5.
7
Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ.细菌钙调蛋白依赖性假激酶 SidJ 催化的蛋白质多聚谷氨酰化。
Elife. 2019 Nov 4;8:e51162. doi: 10.7554/eLife.51162.
8
Systematic Identification of Host Cell Regulators of Legionella pneumophila Pathogenesis Using a Genome-wide CRISPR Screen.利用全基因组 CRISPR 筛选技术系统鉴定肺炎嗜军团菌发病机制的宿主细胞调控因子。
Cell Host Microbe. 2019 Oct 9;26(4):551-563.e6. doi: 10.1016/j.chom.2019.08.017. Epub 2019 Sep 17.
9
Inhibition of bacterial ubiquitin ligases by SidJ-calmodulin catalysed glutamylation.SidJ-钙调蛋白催化的谷氨酸化抑制细菌泛素连接酶。
Nature. 2019 Aug;572(7769):382-386. doi: 10.1038/s41586-019-1440-8. Epub 2019 Jul 22.
10
Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase.钙调蛋白依赖性谷氨酸酶对磷酸核糖泛素化的调节。
Nature. 2019 Aug;572(7769):387-391. doi: 10.1038/s41586-019-1439-1. Epub 2019 Jul 22.