Suppr超能文献

在一系列负载下多聚蛋白的顺序解折叠中捕获的非指数动力学。

Nonexponential kinetics captured in sequential unfolding of polyproteins over a range of loads.

作者信息

Chetrit Einat, Sharma Sabita, Maayan Uri, Pelah Maya Georgia, Klausner Ziv, Popa Ionel, Berkovich Ronen

机构信息

Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.

Department of Physics, University of Wisconsin-Milwaukee, Milwaukee, WI, 53211, USA.

出版信息

Curr Res Struct Biol. 2022 Apr 28;4:106-117. doi: 10.1016/j.crstbi.2022.04.003. eCollection 2022.

Abstract

While performing under mechanical loads , polyproteins are vitally involved in cellular mechanisms such as regulation of tissue elasticity and mechano-transduction by unfolding their comprising domains and extending them. It is widely thought that the process of sequential unfolding of polyproteins follows an exponential kinetics as the individual unfolding events exhibit identical and identically distributed (iid) Poisson behavior. However, it was shown that under high loads, the sequential unfolding kinetics displays nonexponential kinetics that alludes to aging by a subdiffusion process. Statistical order analysis of this kinetics indicated that the individual unfolding events are not iid, and cannot be defined as a Poisson (memoryless) process. Based on numerical simulations it was argued that this behavior becomes less pronounced with lowering the load, therefore it is to be expected that polyproteins unfolding under lower forces will follow a Poisson behavior. This expectation serves as the motivation of the current study, in which we investigate the effect of force lowering on the unfolding kinetics of Poly-L under varying loads, specifically high (150, 100 ​pN) and moderate-low (45, 30, 20 ​pN) forces. We found that a hierarchy among the unfolding events still exists even under low loads, again resulting in nonexponential behavior. We observe that analyzing the dwell-time distributions with stretched-exponentials and power laws give rise to different phenomenological trends. Using statistical order analysis, we demonstrated that even under the lowest load, the sequential unfolding cannot be considered as iid, in accord with the power law distribution. Additional free energy analysis revealed the contribution of the unfolded segments elasticity that scales with the force on the overall one-dimensional contour of the energy landscape, but more importantly, it discloses the hierarchy within the activation barriers during sequential unfolding that account for the observed nonexponentiality.

摘要

在承受机械负荷时,多聚蛋白通过展开其组成结构域并使其伸展,在细胞机制中发挥着至关重要的作用,如调节组织弹性和机械转导。人们普遍认为,多聚蛋白的顺序展开过程遵循指数动力学,因为各个展开事件表现出相同且独立同分布(iid)的泊松行为。然而,研究表明,在高负荷下,顺序展开动力学呈现非指数动力学,这暗示了通过亚扩散过程导致的老化。对这种动力学的统计阶次分析表明,各个展开事件并非iid,且不能定义为泊松(无记忆)过程。基于数值模拟,有人认为随着负荷降低,这种行为会变得不那么明显,因此可以预期在较低力作用下多聚蛋白的展开将遵循泊松行为。这一预期成为本研究的动机,在本研究中,我们研究了力降低对不同负荷下(特别是高负荷:150、100 pN,以及中低负荷:45、30、20 pN)聚-L展开动力学的影响。我们发现,即使在低负荷下,展开事件之间的层次结构仍然存在,再次导致非指数行为。我们观察到,用拉伸指数和幂律分析驻留时间分布会产生不同的现象学趋势。使用统计阶次分析,我们证明即使在最低负荷下,顺序展开也不能被视为iid,这与幂律分布一致。额外的自由能分析揭示了展开片段弹性的贡献,其与能量景观的整体一维轮廓上的力成比例,但更重要的是,它揭示了顺序展开过程中激活屏障内的层次结构,这解释了观察到的非指数性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c77c/9079174/50b44bb20e9a/ga1.jpg

相似文献

1
Nonexponential kinetics captured in sequential unfolding of polyproteins over a range of loads.
Curr Res Struct Biol. 2022 Apr 28;4:106-117. doi: 10.1016/j.crstbi.2022.04.003. eCollection 2022.
2
Correlations within polyprotein forced unfolding dwell-times introduce sequential dependency.
J Struct Biol. 2020 Jun 1;210(3):107495. doi: 10.1016/j.jsb.2020.107495. Epub 2020 Mar 12.
3
Direct observation of markovian behavior of the mechanical unfolding of individual proteins.
Biophys J. 2008 Jul;95(2):782-8. doi: 10.1529/biophysj.107.128298. Epub 2008 Mar 28.
4
Force-clamp analysis techniques give highest rank to stretched exponential unfolding kinetics in ubiquitin.
Biophys J. 2012 Nov 21;103(10):2215-22. doi: 10.1016/j.bpj.2012.10.022. Epub 2012 Nov 20.
5
Interplay between Viscoelasticity and Force Rate Affects Sequential Unfolding in Polyproteins Pulled at Constant Velocity.
Macromolecules. 2020 Apr 28;53(8):3021-3029. doi: 10.1021/acs.macromol.0c00278. Epub 2020 Apr 14.
6
Dwell-time distribution analysis of polyprotein unfolding using force-clamp spectroscopy.
Biophys J. 2007 Apr 15;92(8):2896-903. doi: 10.1529/biophysj.106.099481. Epub 2007 Jan 26.
7
Segmentation and the Entropic Elasticity of Modular Proteins.
J Phys Chem Lett. 2018 Aug 16;9(16):4707-4713. doi: 10.1021/acs.jpclett.8b01925. Epub 2018 Aug 6.
8
Force-clamp spectroscopy of single-protein monomers reveals the individual unfolding and folding pathways of I27 and ubiquitin.
Biophys J. 2007 Oct 1;93(7):2436-46. doi: 10.1529/biophysj.107.104422. Epub 2007 Jun 1.
9
The unfolding kinetics of ubiquitin captured with single-molecule force-clamp techniques.
Proc Natl Acad Sci U S A. 2004 May 11;101(19):7299-304. doi: 10.1073/pnas.0400033101. Epub 2004 Apr 27.
10
Single-molecule force-clamp spectroscopy: dwell time analysis and practical considerations.
Langmuir. 2011 Feb 15;27(4):1440-7. doi: 10.1021/la104130n. Epub 2010 Nov 30.

本文引用的文献

1
Protein nanomechanics in biological context.
Biophys Rev. 2021 Aug 7;13(4):435-454. doi: 10.1007/s12551-021-00822-9. eCollection 2021 Aug.
2
Protein folding modulates the chemical reactivity of a Gram-positive adhesin.
Nat Chem. 2021 Feb;13(2):172-181. doi: 10.1038/s41557-020-00586-x. Epub 2020 Nov 30.
3
Interplay between Viscoelasticity and Force Rate Affects Sequential Unfolding in Polyproteins Pulled at Constant Velocity.
Macromolecules. 2020 Apr 28;53(8):3021-3029. doi: 10.1021/acs.macromol.0c00278. Epub 2020 Apr 14.
4
Mechanical Unfolding of Single Polyubiquitin Molecules Reveals Evidence of Dynamic Disorder.
ACS Omega. 2020 Apr 15;5(16):9104-9113. doi: 10.1021/acsomega.9b03701. eCollection 2020 Apr 28.
5
A HaloTag-TEV genetic cassette for mechanical phenotyping of proteins from tissues.
Nat Commun. 2020 Apr 28;11(1):2060. doi: 10.1038/s41467-020-15465-9.
6
Correlations within polyprotein forced unfolding dwell-times introduce sequential dependency.
J Struct Biol. 2020 Jun 1;210(3):107495. doi: 10.1016/j.jsb.2020.107495. Epub 2020 Mar 12.
8
Titin as a force-generating muscle protein under regulatory control.
J Appl Physiol (1985). 2019 May 1;126(5):1474-1482. doi: 10.1152/japplphysiol.00865.2018. Epub 2018 Dec 6.
9
Modeling Protein-Based Hydrogels under Force.
Phys Rev Lett. 2018 Oct 19;121(16):168101. doi: 10.1103/PhysRevLett.121.168101.
10
Segmentation and the Entropic Elasticity of Modular Proteins.
J Phys Chem Lett. 2018 Aug 16;9(16):4707-4713. doi: 10.1021/acs.jpclett.8b01925. Epub 2018 Aug 6.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验