• 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

细菌应激核苷酸（p）ppGpp 抑制依赖 SRP 的蛋白分泌。

Inhibition of SRP-dependent protein secretion by the bacterial alarmone (p)ppGpp.

机构信息

Center for Synthetic Microbiology (SYNMIKRO) and Department of Chemistry Philipps-Universität Marburg, Marburg, Germany.

Gene Center Munich, Department of Biochemistry, Ludwig-Maximilians-Universität, LMU, Munich, Germany.

出版信息

Nat Commun. 2022 Feb 25;13(1):1069. doi: 10.1038/s41467-022-28675-0.

DOI:10.1038/s41467-022-28675-0
PMID:35217658
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8881573/
Abstract

The stringent response enables bacteria to respond to nutrient limitation and other stress conditions through production of the nucleotide-based second messengers ppGpp and pppGpp, collectively known as (p)ppGpp. Here, we report that (p)ppGpp inhibits the signal recognition particle (SRP)-dependent protein targeting pathway, which is essential for membrane protein biogenesis and protein secretion. More specifically, (p)ppGpp binds to the SRP GTPases Ffh and FtsY, and inhibits the formation of the SRP receptor-targeting complex, which is central for the coordinated binding of the translating ribosome to the SecYEG translocon. Cryo-EM analysis of SRP bound to translating ribosomes suggests that (p)ppGpp may induce a distinct conformational stabilization of the NG domain of Ffh and FtsY in Bacillus subtilis but not in E. coli.

摘要

严格响应使细菌能够通过产生基于核苷酸的第二信使 ppGpp 和 pppGpp（统称为 (p)ppGpp）来应对营养限制和其他应激条件。在这里，我们报告 (p)ppGpp 抑制信号识别颗粒 (SRP) 依赖性蛋白靶向途径，该途径对于膜蛋白生物发生和蛋白分泌是必不可少的。更具体地说，(p)ppGpp 结合到 SRP GTPases Ffh 和 FtsY，并抑制 SRP 受体靶向复合物的形成，该复合物对于协调翻译核糖体与 SecYEG 易位酶的结合至关重要。结合到翻译核糖体的 SRP 的冷冻电镜分析表明，(p)ppGpp 可能诱导枯草芽孢杆菌中 Ffh 和 FtsY 的 NG 结构域发生独特的构象稳定，但在大肠杆菌中则不会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/ecf9a5771d62/41467_2022_28675_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/11f3696bc155/41467_2022_28675_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/3fa40146e3cb/41467_2022_28675_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/c874719157f3/41467_2022_28675_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/57dd386c6e85/41467_2022_28675_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/ad3905415a52/41467_2022_28675_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/ecf9a5771d62/41467_2022_28675_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/11f3696bc155/41467_2022_28675_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/3fa40146e3cb/41467_2022_28675_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/c874719157f3/41467_2022_28675_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/57dd386c6e85/41467_2022_28675_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/ad3905415a52/41467_2022_28675_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d819/8881573/ecf9a5771d62/41467_2022_28675_Fig6_HTML.jpg

相似文献

1
Inhibition of SRP-dependent protein secretion by the bacterial alarmone (p)ppGpp.细菌应激核苷酸（p）ppGpp 抑制依赖 SRP 的蛋白分泌。
Nat Commun. 2022 Feb 25;13(1):1069. doi: 10.1038/s41467-022-28675-0.
2
The bacterial SRP receptor, FtsY, is activated on binding to the translocon.细菌信号识别颗粒受体FtsY与易位子结合后被激活。
Mol Microbiol. 2016 Oct;102(1):152-67. doi: 10.1111/mmi.13452. Epub 2016 Jul 19.
3
Cryo-EM structure of the E. coli translating ribosome in complex with SRP and its receptor.大肠杆菌翻译核糖体与 SRP 和其受体复合物的冷冻电镜结构
Nat Struct Mol Biol. 2011 Jan;18(1):88-90. doi: 10.1038/nsmb.1952. Epub 2010 Dec 12.
4
Predominant membrane localization is an essential feature of the bacterial signal recognition particle receptor.主要膜定位是细菌信号识别颗粒受体的一个基本特征。
BMC Biol. 2009 Nov 13;7:76. doi: 10.1186/1741-7007-7-76.
5
Signal sequence-independent SRP-SR complex formation at the membrane suggests an alternative targeting pathway within the SRP cycle.在膜上形成与信号序列无关的 SRP-SR 复合物表明了 SRP 循环内的一种替代靶向途径。
Mol Biol Cell. 2011 Jul 1;22(13):2309-23. doi: 10.1091/mbc.E11-02-0152. Epub 2011 May 5.
6
Membrane protein biogenesis in Ffh- or FtsY-depleted Escherichia coli.在 Ffh 或 FtsY 耗尽的大肠杆菌中膜蛋白的生物发生。
PLoS One. 2010 Feb 9;5(2):e9130. doi: 10.1371/journal.pone.0009130.
7
Domain rearrangement of SRP protein Ffh upon binding 4.5S RNA and the SRP receptor FtsY.信号识别颗粒（SRP）蛋白Ffh与4.5S RNA及SRP受体FtsY结合后发生的结构域重排
RNA. 2005 Jun;11(6):947-57. doi: 10.1261/rna.7242305.
8
Conformational changes in the bacterial SRP receptor FtsY upon binding of guanine nucleotides and SRP.鸟嘌呤核苷酸和信号识别颗粒（SRP）结合后细菌SRP受体FtsY的构象变化
J Mol Biol. 2000 Jan 28;295(4):745-53. doi: 10.1006/jmbi.1999.3427.
9
Accumulation of endoplasmic membranes and novel membrane-bound ribosome-signal recognition particle receptor complexes in Escherichia coli.内质网膜和新型膜结合核糖体-信号识别颗粒受体复合物在大肠杆菌中的积累。
J Cell Biol. 2002 Nov 11;159(3):403-10. doi: 10.1083/jcb.200204144. Epub 2002 Nov 4.
10
Structural basis of signal sequence surveillance and selection by the SRP-FtsY complex.SRP-FtsY 复合物对信号序列监控和选择的结构基础。
Nat Struct Mol Biol. 2013 May;20(5):604-10. doi: 10.1038/nsmb.2546. Epub 2013 Apr 7.

引用本文的文献

1
Food colorant brilliant blue causes persistent functional and structural changes in an in vitro simplified microbiota model system.食用色素亮蓝在体外简化微生物群模型系统中引起持续的功能和结构变化。
ISME Commun. 2025 Mar 22;5(1):ycaf050. doi: 10.1093/ismeco/ycaf050. eCollection 2025 Jan.
2
Peroxisomal core structures segregate diverse metabolic pathways.过氧化物酶体核心结构分隔多种代谢途径。
Nat Commun. 2025 Feb 20;16(1):1802. doi: 10.1038/s41467-025-57053-9.
3
Structural and mechanistic basis for the regulation of the chloroplast signal recognition particle by (p)ppGpp.

本文引用的文献

1
(p)ppGpp controls stringent factors by exploiting antagonistic allosteric coupling between catalytic domains.(p)ppGpp 通过利用催化结构域之间的拮抗变构偶联来控制严格因子。
Mol Cell. 2021 Aug 19;81(16):3310-3322.e6. doi: 10.1016/j.molcel.2021.07.026.
2
Two P or Not Two P: Understanding Regulation by the Bacterial Second Messengers (p)ppGpp.双磷酸鸟苷或非双磷酸鸟苷：理解细菌第二信使（p）ppGpp的调控作用
Annu Rev Microbiol. 2021 Oct 8;75:383-406. doi: 10.1146/annurev-micro-042621-122343. Epub 2021 Aug 3.
3
Structural Basis for Regulation of the Opposing (p)ppGpp Synthetase and Hydrolase within the Stringent Response Orchestrator Rel.
（p）ppGpp对叶绿体信号识别颗粒调控的结构和机制基础
FEBS Lett. 2025 May;599(10):1373-1385. doi: 10.1002/1873-3468.70008. Epub 2025 Feb 11.
4
Inorganic polyphosphate and the stringent response coordinately control cell division and cell morphology in .无机多聚磷酸盐与严谨反应协同控制……中的细胞分裂和细胞形态。 （注：原文句末“in”后面缺少具体内容）
mBio. 2025 Feb 5;16(2):e0351124. doi: 10.1128/mbio.03511-24. Epub 2024 Dec 27.
5
Inorganic polyphosphate and the stringent response coordinately control cell division and cell morphology in .无机多聚磷酸盐与严谨反应协同控制……中的细胞分裂和细胞形态。 （原文中“in.”后面内容缺失）
bioRxiv. 2024 Sep 12:2024.09.11.612536. doi: 10.1101/2024.09.11.612536.
6
Control of a chemical chaperone by a universally conserved ATPase.一种普遍保守的ATP酶对化学伴侣的调控
iScience. 2024 Jun 8;27(7):110215. doi: 10.1016/j.isci.2024.110215. eCollection 2024 Jul 19.
7
produces (p)ppGpp in response to the bacteriostatic antibiotic chloramphenicol to prevent its potential bactericidal effect.在受到抑菌抗生素氯霉素刺激时产生（p）ppGpp，以防止其潜在的杀菌作用。
mLife. 2022 Jun 30;1(2):101-113. doi: 10.1002/mlf2.12031. eCollection 2022 Jun.
8
"Metabolic burden" explained: stress symptoms and its related responses induced by (over)expression of (heterologous) proteins in Escherichia coli.“代谢负担”解析：大肠杆菌中（过）表达（异源）蛋白所诱导的应激症状及其相关反应。
Microb Cell Fact. 2024 Mar 30;23(1):96. doi: 10.1186/s12934-024-02370-9.
9
(p)ppGpp - an important player during heat shock response.（p）ppGpp——热休克反应中的一个重要参与者。
Microlife. 2023 Apr 6;4:uqad017. doi: 10.1093/femsml/uqad017. eCollection 2023.
10
Recent advances and perspectives in nucleotide second messenger signaling in bacteria.细菌中核苷酸第二信使信号传导的最新进展与展望
Microlife. 2023 Apr 17;4:uqad015. doi: 10.1093/femsml/uqad015. eCollection 2023.
结构基础调节严格反应协调蛋白 Rel 中（p）ppGpp 合成酶和水解酶的活性。
Cell Rep. 2020 Sep 15;32(11):108157. doi: 10.1016/j.celrep.2020.108157.
4
The alarmones (p)ppGpp directly regulate translation initiation during entry into quiescence.警报素（p）ppGpp 直接调控进入休眠期时的翻译起始。
Proc Natl Acad Sci U S A. 2020 Jul 7;117(27):15565-15572. doi: 10.1073/pnas.1920013117. Epub 2020 Jun 23.
5
A nucleotide-switch mechanism mediates opposing catalytic activities of Rel enzymes.核苷酸开关机制介导 Rel 酶的相反催化活性。
Nat Chem Biol. 2020 Aug;16(8):834-840. doi: 10.1038/s41589-020-0520-2. Epub 2020 May 11.
6
The alarmones (p)ppGpp are part of the heat shock response of Bacillus subtilis.警报素 (p)ppGpp 是枯草芽孢杆菌热休克反应的一部分。
PLoS Genet. 2020 Mar 16;16(3):e1008275. doi: 10.1371/journal.pgen.1008275. eCollection 2020 Mar.
7
Estimation of high-order aberrations and anisotropic magnification from cryo-EM data sets in -3.1.从-3.1中的冷冻电镜数据集估计高阶像差和各向异性放大率。
IUCrJ. 2020 Feb 11;7(Pt 2):253-267. doi: 10.1107/S2052252520000081. eCollection 2020 Mar 1.
8
The (p)ppGpp-binding GTPase Era promotes rRNA processing and cold adaptation in Staphylococcus aureus.(p)ppGpp 结合 GTP 酶 Era 促进金黄色葡萄球菌的 rRNA 加工和冷适应。
PLoS Genet. 2019 Aug 29;15(8):e1008346. doi: 10.1371/journal.pgen.1008346. eCollection 2019 Aug.
9
Analysis of nucleotide pools in bacteria using HPLC-MS in HILIC mode.采用 HPLC-MS 在 HILIC 模式下分析细菌中的核苷酸池。
Talanta. 2019 Dec 1;205:120161. doi: 10.1016/j.talanta.2019.120161. Epub 2019 Jul 18.
10
Structure, dynamics and interactions of large SRP variants.大型 SRP 变体的结构、动态和相互作用。
Biol Chem. 2019 Dec 18;401(1):63-80. doi: 10.1515/hsz-2019-0282.