ssrA降解标签内重叠的识别决定簇可调节蛋白水解作用。
Overlapping recognition determinants within the ssrA degradation tag allow modulation of proteolysis.
作者信息
Flynn J M, Levchenko I, Seidel M, Wickner S H, Sauer R T, Baker T A
机构信息
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10584-9. doi: 10.1073/pnas.191375298. Epub 2001 Sep 4.
Abstract
The ssrA tag, an 11-aa peptide added to the C terminus of proteins stalled during translation, targets proteins for degradation by ClpXP and ClpAP. Mutational analysis of the ssrA tag reveals independent, but overlapping determinants for its interactions with ClpX, ClpA, and SspB, a specificity-enhancing factor for ClpX. ClpX interacts with residues 9-11 at the C terminus of the tag, whereas ClpA recognizes positions 8-10 in addition to residues 1-2 at the N terminus. SspB interacts with residues 1-4 and 7, N-terminal to the ClpX-binding determinants, but overlapping the ClpA determinants. As a result, SspB and ClpX work together to recognize ssrA-tagged substrates efficiently, whereas SspB inhibits recognition of these substrates by ClpA. Thus, dissection of the recognition signals within the ssrA tag provides insight into how multiple proteins function in concert to modulate proteolysis.
摘要
ssrA标签是一种在翻译过程中停滞的蛋白质C末端添加的11个氨基酸的肽，它将蛋白质靶向由ClpXP和ClpAP进行降解。对ssrA标签的突变分析揭示了其与ClpX、ClpA和SspB（一种ClpX的特异性增强因子）相互作用的独立但重叠的决定因素。ClpX与标签C末端的9-11位残基相互作用，而ClpA除了识别N末端的1-2位残基外，还识别8-10位。SspB与ClpX结合决定因素N末端的1-4位和7位残基相互作用，但与ClpA决定因素重叠。因此，SspB和ClpX共同作用以有效识别带有ssrA标签的底物，而SspB抑制ClpA对这些底物的识别。因此，剖析ssrA标签内的识别信号有助于深入了解多种蛋白质如何协同作用来调节蛋白水解。
相似文献
1
Overlapping recognition determinants within the ssrA degradation tag allow modulation of proteolysis.ssrA降解标签内重叠的识别决定簇可调节蛋白水解作用。
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10584-9. doi: 10.1073/pnas.191375298. Epub 2001 Sep 4.
2
SspB delivery of substrates for ClpXP proteolysis probed by the design of improved degradation tags.通过设计改进的降解标签探究SspB介导的底物向ClpXP蛋白酶体的传递。
Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12136-41. doi: 10.1073/pnas.0404733101. Epub 2004 Aug 5.
3
The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system.ClpXP蛋白酶和ClpAP蛋白酶可降解由SsrA标记系统添加了羧基末端肽尾的蛋白质。
Genes Dev. 1998 May 1;12(9):1338-47. doi: 10.1101/gad.12.9.1338.
4
Targeted delivery of an ssrA-tagged substrate by the adaptor protein SspB to its cognate AAA+ protein ClpX.衔接蛋白SspB将带有ssrA标签的底物靶向递送至其同源的AAA+蛋白ClpX。
Mol Cell. 2003 Aug;12(2):373-80. doi: 10.1016/j.molcel.2003.08.012.
5
An intrinsic degradation tag on the ClpA C-terminus regulates the balance of ClpAP complexes with different substrate specificity.ClpA 蛋白 C 端的一个内在降解标签调节具有不同底物特异性的 ClpAP 复合物的平衡。
J Mol Biol. 2008 Dec 12;384(2):503-11. doi: 10.1016/j.jmb.2008.09.046. Epub 2008 Sep 26.
6
Cytoplasmic degradation of ssrA-tagged proteins.带有ssrA标签的蛋白质的细胞质降解
Mol Microbiol. 2005 Sep;57(6):1750-61. doi: 10.1111/j.1365-2958.2005.04798.x.
7
Characterization of a specificity factor for an AAA+ ATPase: assembly of SspB dimers with ssrA-tagged proteins and the ClpX hexamer.一种AAA+ ATP酶特异性因子的特性：SspB二聚体与带有ssrA标签的蛋白质及ClpX六聚体的组装
Chem Biol. 2002 Nov;9(11):1237-45. doi: 10.1016/s1074-5521(02)00268-5.
8
Flexible linkers leash the substrate binding domain of SspB to a peptide module that stabilizes delivery complexes with the AAA+ ClpXP protease.柔性接头将SspB的底物结合结构域拴系到一个肽模块上，该肽模块可稳定与AAA+ ClpXP蛋白酶形成的递送复合物。
Mol Cell. 2003 Aug;12(2):355-63. doi: 10.1016/s1097-2765(03)00272-7.
9
ClpAP and ClpXP degrade proteins with tags located in the interior of the primary sequence.ClpAP和ClpXP会降解那些标签位于一级序列内部的蛋白质。
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11037-42. doi: 10.1073/pnas.172378899. Epub 2002 Aug 12.
10
Modulating substrate choice: the SspB adaptor delivers a regulator of the extracytoplasmic-stress response to the AAA+ protease ClpXP for degradation.调节底物选择：SspB衔接蛋白将胞外应激反应的调节因子递送至AAA+蛋白酶ClpXP进行降解。
Genes Dev. 2004 Sep 15;18(18):2292-301. doi: 10.1101/gad.1240104.
引用本文的文献
1
Engineering of photo-inducible binary interaction tools for biomedical applications.用于生物医学应用的光诱导二元相互作用工具的工程设计。
Nat Commun. 2025 Jul 28;16(1):6940. doi: 10.1038/s41467-025-61710-4.
2
The final proteolytic step in transmembrane signaling of multiple RsgI anti-σ factors in Clostridium thermocellum.嗜热栖热放线菌中多种RsgI抗σ因子跨膜信号传导的最终蛋白水解步骤。
Biosci Rep. 2025 Apr 9;45(4):233-45. doi: 10.1042/BSR20253055.
3
Engineering a New SsrA-Based Degradation Tag (LAA-LAA) and a Bacterial Synthetic Oscillator.设计一种新型基于SsrA的降解标签（LAA-LAA）和一种细菌合成振荡器。
ACS Synth Biol. 2025 Apr 18;14(4):1062-1071. doi: 10.1021/acssynbio.4c00612. Epub 2025 Mar 19.
4
Cell Sizes Matter for Industrial Bioproduction, a Case of Polyhydroxybutyrate.细胞大小对工业生物生产至关重要——以聚羟基丁酸酯为例。
Adv Sci (Weinh). 2025 Apr;12(14):e2412256. doi: 10.1002/advs.202412256. Epub 2025 Feb 18.
5
Capsular polysaccharide restrains type VI secretion in .荚膜多糖抑制……中的VI型分泌系统。 （原文句子不完整，推测补充后的完整译文是这样，但请根据实际完整原文进行准确理解。）
Elife. 2025 Jan 3;14:e101032. doi: 10.7554/eLife.101032.
6
How the double-ring ClpAP protease motor grips the substrate to unfold and degrade stable proteins.双环ClpAP蛋白酶马达如何抓住底物以展开并降解稳定蛋白质。
J Biol Chem. 2024 Nov;300(11):107861. doi: 10.1016/j.jbc.2024.107861. Epub 2024 Oct 5.
7
Expanding the genetic toolbox for the obligate human pathogen .扩展专性人类病原体的基因工具库。
Front Bioeng Biotechnol. 2024 Jun 7;12:1395659. doi: 10.3389/fbioe.2024.1395659. eCollection 2024.
8
A role for the S4-domain containing protein YlmH in ribosome-associated quality control in Bacillus subtilis.S4 结构域蛋白 YlmH 在枯草芽孢杆菌核糖体相关质量控制中的作用。
Nucleic Acids Res. 2024 Aug 12;52(14):8483-8499. doi: 10.1093/nar/gkae399.
9
Proteolytic stability and aggregation in a key metabolic enzyme of bacteria.细菌关键代谢酶的蛋白水解稳定性和聚集。
Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2301458121. doi: 10.1073/pnas.2301458121. Epub 2024 Apr 29.
10
Toxin-based screening of C-terminal tags in reveals the exceptional potency of ssrA-like degrons.基于毒素的C端标签筛选揭示了类ssrA降解子的超强效力。
bioRxiv. 2024 Apr 12:2024.01.29.576913. doi: 10.1101/2024.01.29.576913.
本文引用的文献
1
The RssB response regulator directly targets sigma(S) for degradation by ClpXP.RssB反应调节因子直接靶向σ(S)，使其被ClpXP降解。
Genes Dev. 2001 Mar 1;15(5):627-37. doi: 10.1101/gad.864401.
2
Visualization of substrate binding and translocation by the ATP-dependent protease, ClpXP.通过ATP依赖性蛋白酶ClpXP对底物结合和易位的可视化。
Mol Cell. 2000 Dec;6(6):1515-21. doi: 10.1016/s1097-2765(00)00148-9.
3
Subunit-specific degradation of the UmuD/D' heterodimer by the ClpXP protease: the role of trans recognition in UmuD' stability.ClpXP蛋白酶对UmuD/D'异源二聚体的亚基特异性降解：反式识别在UmuD'稳定性中的作用。
EMBO J. 2000 Oct 2;19(19):5251-8. doi: 10.1093/emboj/19.19.5251.
4
A specificity-enhancing factor for the ClpXP degradation machine.一种用于ClpXP降解机器的特异性增强因子。
Science. 2000 Sep 29;289(5488):2354-6. doi: 10.1126/science.289.5488.2354.
5
Substrate recognition by the ClpA chaperone component of ClpAP protease.ClpAP蛋白酶的伴侣蛋白组分ClpA对底物的识别
J Biol Chem. 2000 Nov 10;275(45):35361-7. doi: 10.1074/jbc.M006288200.
6
Protein binding and unfolding by the chaperone ClpA and degradation by the protease ClpAP.伴侣蛋白ClpA介导的蛋白质结合与去折叠以及蛋白酶ClpAP介导的蛋白质降解
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8892-7. doi: 10.1073/pnas.97.16.8892.
7
Dynamics of substrate denaturation and translocation by the ClpXP degradation machine.ClpXP降解机器介导的底物变性与转运动力学
Mol Cell. 2000 Apr;5(4):639-48. doi: 10.1016/s1097-2765(00)80243-9.
8
The 26S proteasome: a molecular machine designed for controlled proteolysis.26S蛋白酶体：一种专为可控蛋白水解而设计的分子机器。
Annu Rev Biochem. 1999;68:1015-68. doi: 10.1146/annurev.biochem.68.1.1015.
9
Substrate recognition through a PDZ domain in tail-specific protease.通过尾部特异性蛋白酶中的PDZ结构域进行底物识别。
Biochemistry. 2000 Mar 21;39(11):3149-55. doi: 10.1021/bi992709s.
10
Addiction modules and programmed cell death and antideath in bacterial cultures.细菌培养中的成瘾模块、程序性细胞死亡和抗死亡
Annu Rev Microbiol. 1999;53:43-70. doi: 10.1146/annurev.micro.53.1.43.
Zotero 插件