Cleaning the molecular machinery of cells via proteostasis, proteolysis and endocytosis selectively, effectively, and precisely: intracellular self-defense and cellular perturbations,Molecular Omics

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Cleaning the molecular machinery of cells via proteostasis, proteolysis and endocytosis selectively, effectively, and precisely: intracellular self-defense and cellular perturbations
Molecular Omics ( IF 3.0 ) Pub Date : 2020-11-2 , DOI: 10.1039/d0mo00085j
Rajiv Kumar ₁ , Bhupender S Chhikara , Kiran Gulia , Mitrabasu Chhillar

Affiliation

Network coordinates of cellular processes (proteostasis, proteolysis, and endocytosis), and molecular chaperones are the key complements in the cell machinery and processes. Specifically, cellular pathways are responsible for the conformational maintenance, cellular concentration, interactions, protein synthesis, disposal of misfolded proteins, localization, folding, and degradation. The failure of cellular processes and pathways disturbs structural proteins and the nucleation of amyloids. These mishaps further initiate amyloid polymorphism, transmissibility, co-aggregation of pathogenic proteins in tissues and cells, prion strains, and mechanisms and pathways for toxicity. Consequently, these conditions favor and lead to the formation of elongated amyloid fibrils consisting of many-stranded β-sheets (N,N-terminus and C,C-terminus), and abnormal fibrous, extracellular, proteinaceous deposits. Finally, these β-sheets deposit, and cells fail to degrade them effectively. The essential torsion angles (φ, ψ, and ω) define the conformation of proteins and their architecture. Cells initiate several transformations and pathways during the regulation of protein homeostasis based on the requirements for the functioning of the cell, which are governed by ATP-dependent proteases. In this process, the kinetics of the molding/folding phenomenon is disturbed, and subsequently, it is dominated by cross-domain misfolding intermediates; however, simultaneously, it is opposed by small stretching forces, which naturally exist in the cell. The ubiquitin/proteasome system deals with damaged proteins, which are not refolded by the chaperone-type machinery. Ubiquitin-protein ligases (E3-Ub) participate in all the cellular activity initiated and governed by molecular chaperones to stabilize the cellular proteome and participate in the degradation phenomenon implemented for damaged proteins. Optical tweezers, a single-resolution based technique, disclose the folding pathway of linear chain proteins, which is how they convert themselves into a three-dimensional architecture. Further, DNA–protein conjugation analysis is performed to obtain folding energies as single-molecule kinetic and thermodynamic data.

中文翻译：

通过蛋白稳态、蛋白水解和内吞作用选择性、有效和精确地清洁细胞的分子机制：细胞内自卫和细胞扰动

细胞过程（蛋白稳态、蛋白水解和内吞作用）和分子伴侣的网络坐标是细胞机制和过程的关键补充。具体而言，细胞通路负责构象维持、细胞浓度、相互作用、蛋白质合成、错误折叠蛋白质的处理、定位、折叠和降解。细胞过程和途径的失败会扰乱结构蛋白和淀粉样蛋白的成核。这些事故进一步引发了淀粉样蛋白多态性、可传播性、组织和细胞中致病蛋白的共聚集、朊病毒菌株以及毒性机制和途径。因此，这些条件有利于并导致由多链β-折叠（N，N-末端和C，C-末端）组成的细长淀粉样原纤维的形成，以及异常的纤维、细胞外、蛋白质沉积物。最后，这些β-折叠沉积，细胞无法有效降解它们。基本扭转角（φ、ψ和ω) 定义蛋白质的构象及其结构。根据细胞功能的要求，细胞在蛋白质稳态调节期间启动多种转化和途径，这些转化和途径由 ATP 依赖性蛋白酶控制。在这个过程中，成型/折叠现象的动力学受到干扰，随后，它被跨域错误折叠中间体所支配；然而，与此同时，它受到细胞中自然存在的小拉伸力的反对。泛素/蛋白酶体系统处理受损的蛋白质，这些蛋白质不会被伴侣型机器重新折叠。泛素-蛋白质连接酶 (E3-Ub) 参与由分子伴侣启动和控制的所有细胞活动，以稳定细胞蛋白质组并参与对受损蛋白质实施的降解现象。光镊是一种基于单分辨率的技术，揭示了线性链蛋白的折叠途径，这就是它们如何将自身转化为三维结构。此外，进行DNA-蛋白质缀合分析以获得折叠能作为单分子动力学和热力学数据。

更新日期：2020-12-09

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