独特的接触引导AAA+解折叠酶ClpX对四聚体Mu转座酶-DNA复合物进行高优先级识别。
Unique contacts direct high-priority recognition of the tetrameric Mu transposase-DNA complex by the AAA+ unfoldase ClpX.
作者信息
Abdelhakim Aliaa H, Oakes Elizabeth C, Sauer Robert T, Baker Tania A
机构信息
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Mol Cell. 2008 Apr 11;30(1):39-50. doi: 10.1016/j.molcel.2008.02.013.
Abstract
Clp/Hsp100 ATPases remodel and disassemble multiprotein complexes, yet little is known about how they preferentially recognize these complexes rather than their constituent subunits. We explore how substrate multimerization modulates recognition by the ClpX unfoldase using a natural substrate, MuA transposase. MuA is initially monomeric but forms a stable tetramer when bound to transposon DNA. Destabilizing this tetramer by ClpX promotes an essential transition in the phage Mu recombination pathway. We show that ClpX interacts more tightly with tetrameric than with monomeric MuA. Residues exposed only in the MuA tetramer are important for enhanced recognition--which requires the N domain of ClpX--as well as for a high maximal disassembly rate. We conclude that an extended set of potential enzyme contacts are exposed upon assembly of the tetramer and function as internal guides to recruit ClpX, thereby ensuring that the tetrameric complex is a high-priority substrate.
摘要
Clp/Hsp100 ATP酶可重塑并拆解多蛋白复合物，但对于它们如何优先识别这些复合物而非其组成亚基，我们却知之甚少。我们利用天然底物MuA转座酶，探究底物多聚化如何调节ClpX解折叠酶的识别过程。MuA最初是单体，但与转座子DNA结合时会形成稳定的四聚体。ClpX使该四聚体不稳定，从而促进噬菌体Mu重组途径中的关键转变。我们发现，ClpX与四聚体MuA的相互作用比与单体MuA更为紧密。仅在MuA四聚体中暴露的残基对于增强识别（这需要ClpX的N结构域）以及高最大拆解速率很重要。我们得出结论，四聚体组装时会暴露一组扩展的潜在酶接触位点，并作为内部引导物来招募ClpX，从而确保四聚体复合物是高优先级底物。
相似文献
1
Unique contacts direct high-priority recognition of the tetrameric Mu transposase-DNA complex by the AAA+ unfoldase ClpX.独特的接触引导AAA+解折叠酶ClpX对四聚体Mu转座酶-DNA复合物进行高优先级识别。
Mol Cell. 2008 Apr 11;30(1):39-50. doi: 10.1016/j.molcel.2008.02.013.
2
The AAA+ ClpX machine unfolds a keystone subunit to remodel the Mu transpososome.AAA+ ClpX 机器展开关键亚基来重塑 Mu 转座子。
Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2437-42. doi: 10.1073/pnas.0910905106. Epub 2010 Jan 25.
3
Remodeling protein complexes: insights from the AAA+ unfoldase ClpX and Mu transposase.重塑蛋白复合物：来自AAA+解折叠酶ClpX和Mu转座酶的见解
Protein Sci. 2005 Aug;14(8):1945-54. doi: 10.1110/ps.051417505.
4
Deciphering the Roles of Multicomponent Recognition Signals by the AAA+ Unfoldase ClpX.由AAA+解折叠酶ClpX解析多组分识别信号的作用。
J Mol Biol. 2015 Sep 11;427(18):2966-82. doi: 10.1016/j.jmb.2015.03.008. Epub 2015 Mar 19.
5
ClpX-mediated remodeling of mu transpososomes: selective unfolding of subunits destabilizes the entire complex.ClpX介导的μ转座体重塑：亚基的选择性解折叠使整个复合物不稳定。
Mol Cell. 2001 Aug;8(2):449-54. doi: 10.1016/s1097-2765(01)00307-0.
6
Specificity in substrate and cofactor recognition by the N-terminal domain of the chaperone ClpX.伴侣蛋白ClpX的N端结构域对底物和辅因子识别的特异性
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17724-9. doi: 10.1073/pnas.0601505103. Epub 2006 Nov 7.
7
Disassembly of the Mu transposase tetramer by the ClpX chaperone.通过ClpX伴侣蛋白使Mu转座酶四聚体解聚。
Genes Dev. 1995 Oct 1;9(19):2399-408. doi: 10.1101/gad.9.19.2399.
8
Diverse pore loops of the AAA+ ClpX machine mediate unassisted and adaptor-dependent recognition of ssrA-tagged substrates.AAA+ ClpX 机器的多种孔环介导对带有 ssrA 标签底物的无辅助识别和依赖衔接子的识别。
Mol Cell. 2008 Feb 29;29(4):441-50. doi: 10.1016/j.molcel.2008.02.002.
9
Mu transpososome architecture ensures that unfolding by ClpX or proteolysis by ClpXP remodels but does not destroy the complex.Mu转座体结构确保通过ClpX展开或通过ClpXP进行蛋白水解可重塑但不会破坏该复合物。
Chem Biol. 2003 May;10(5):463-72. doi: 10.1016/s1074-5521(03)00102-9.
10
Pore loops of the AAA+ ClpX machine grip substrates to drive translocation and unfolding.AAA+ ClpX 机器的孔环抓住底物以驱动易位和解折叠。
Nat Struct Mol Biol. 2008 Nov;15(11):1147-51. doi: 10.1038/nsmb.1503. Epub 2008 Oct 19.
引用本文的文献
1
Elucidating the Architectural dynamics of MuB filaments in bacteriophage Mu DNA transposition.阐明噬菌体 Mu DNA 转位中 MuB 丝的结构动力学。
Nat Commun. 2024 Jul 31;15(1):6445. doi: 10.1038/s41467-024-50722-1.
2
Targeted DNA integration in human cells without double-strand breaks using CRISPR RNA-guided transposases.使用CRISPR RNA引导转座酶在人类细胞中实现无双链断裂的靶向DNA整合。
bioRxiv. 2023 Mar 18:2023.03.17.533036. doi: 10.1101/2023.03.17.533036.
3
Targeted DNA integration in human cells without double-strand breaks using CRISPR-associated transposases.利用 CRISPR 相关转座酶在人类细胞中进行靶向 DNA 整合，而无需双链断裂。
Nat Biotechnol. 2024 Jan;42(1):87-98. doi: 10.1038/s41587-023-01748-1. Epub 2023 Mar 29.
4
An enhancer sequence in the intrinsically disordered region of FtsZ promotes polymer-guided substrate processing by ClpXP protease.FtsZ 无规卷曲区域中的增强子序列促进 ClpXP 蛋白酶对底物的聚合物导向加工。
Protein Sci. 2022 May;31(5):e4306. doi: 10.1002/pro.4306.
5
Mu transpososome activity-profiling yields hyperactive MuA variants for highly efficient genetic and genome engineering.Mu 转座子活性分析产生超活性 MuA 变体，用于高效的遗传和基因组工程。
Nucleic Acids Res. 2018 May 18;46(9):4649-4661. doi: 10.1093/nar/gkx1281.
6
The Protein Chaperone ClpX Targets Native and Non-native Aggregated Substrates for Remodeling, Disassembly, and Degradation with ClpP.蛋白质伴侣ClpX靶向天然和非天然聚集底物，与ClpP一起进行重塑、拆解和降解。
Front Mol Biosci. 2017 May 4;4:26. doi: 10.3389/fmolb.2017.00026. eCollection 2017.
7
Strain-Dependent Recognition of a Unique Degradation Motif by ClpXP in .ClpXP对独特降解基序的菌株依赖性识别 于……中
mSphere. 2016 Dec 7;1(6). doi: 10.1128/mSphere.00287-16. eCollection 2016 Nov-Dec.
8
Engineered AAA+ proteases reveal principles of proteolysis at the mitochondrial inner membrane.工程化 AAA+ 蛋白酶揭示了线粒体内膜蛋白水解的原理。
Nat Commun. 2016 Oct 27;7:13301. doi: 10.1038/ncomms13301.
9
Oxidization without substrate unfolding triggers proteolysis of the peroxide-sensor, PerR.无底物解折叠的氧化作用会引发过氧化物传感器PerR的蛋白水解。
Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):E23-31. doi: 10.1073/pnas.1522687112. Epub 2015 Dec 17.
10
Transposable Phage Mu.可转移噬菌体 Mu
Microbiol Spectr. 2014 Oct;2(5). doi: 10.1128/microbiolspec.MDNA3-0007-2014.
本文引用的文献
1
Structural basis of SspB-tail recognition by the zinc binding domain of ClpX.ClpX锌结合结构域识别SspB尾部的结构基础。
J Mol Biol. 2007 Mar 23;367(2):514-26. doi: 10.1016/j.jmb.2007.01.003. Epub 2007 Jan 9.
2
Specificity in substrate and cofactor recognition by the N-terminal domain of the chaperone ClpX.伴侣蛋白ClpX的N端结构域对底物和辅因子识别的特异性
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17724-9. doi: 10.1073/pnas.0601505103. Epub 2006 Nov 7.
3
ATP-dependent proteases of bacteria: recognition logic and operating principles.细菌的ATP依赖性蛋白酶：识别逻辑与作用原理
Trends Biochem Sci. 2006 Dec;31(12):647-53. doi: 10.1016/j.tibs.2006.10.006. Epub 2006 Oct 30.
4
Engineering controllable protein degradation.工程化可控蛋白质降解
Mol Cell. 2006 Jun 9;22(5):701-7. doi: 10.1016/j.molcel.2006.04.027.
5
The amino-terminal domain of ClpB supports binding to strongly aggregated proteins.ClpB的氨基末端结构域支持与高度聚集的蛋白质结合。
J Biol Chem. 2005 Oct 14;280(41):34940-5. doi: 10.1074/jbc.M505653200. Epub 2005 Aug 2.
6
AAA+ proteins: have engine, will work.AAA+蛋白：有动力，就能发挥作用。
Nat Rev Mol Cell Biol. 2005 Jul;6(7):519-29. doi: 10.1038/nrm1684.
7
Remodeling protein complexes: insights from the AAA+ unfoldase ClpX and Mu transposase.重塑蛋白复合物：来自AAA+解折叠酶ClpX和Mu转座酶的见解
Protein Sci. 2005 Aug;14(8):1945-54. doi: 10.1110/ps.051417505.
8
3D reconstruction of the Mu transposase and the Type 1 transpososome: a structural framework for Mu DNA transposition.Mu转座酶与1型转座体的三维重建：Mu DNA转座的结构框架。
Genes Dev. 2005 Apr 1;19(7):840-52. doi: 10.1101/gad.1291405. Epub 2005 Mar 17.
9
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.
10
V(D)J recombination: how to tame a transposase.V(D)J重排：如何驯化转座酶
Immunol Rev. 2004 Aug;200:249-60. doi: 10.1111/j.0105-2896.2004.00161.x.
Zotero 插件