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Proteostasis is adaptive: Balancing chaperone holdases against foldases
PLOS Computational Biology ( IF 3.8 ) Pub Date : 2020-12-14 , DOI: 10.1371/journal.pcbi.1008460
Adam MR de Graff , David E. Mosedale , Tilly Sharp , Ken A. Dill , David J. Grainger

Because a cell must adapt to different stresses and growth rates, its proteostasis system must too. How do cells detect and adjust proteome folding to different conditions? Here, we explore a biophysical cost-benefit principle, namely that the cell should keep its proteome as folded as possible at the minimum possible energy cost. This can be achieved by differential expression of chaperones–balancing foldases (which accelerate folding) against holdases (which act as parking spots). The model captures changes in the foldase-holdase ratio observed both within organisms during aging and across organisms of varying metabolic rates. This work describes a simple biophysical mechanism by which cellular proteostasis adapts to meet the needs of a changing growth environment.



中文翻译:

蛋白质变形是适应性的:平衡伴侣保持酶与折叠酶

由于细胞必须适应不同的压力和生长速率,因此其蛋白质稳态系统也必须如此。细胞如何检测和调整蛋白质组折叠以适应不同条件?在这里,我们探讨了一种生物物理成本收益原理,即该细胞应以最小的能量成本保持其蛋白质组尽可能折叠。这可以通过伴侣蛋白平衡表达折叠酶(促进折叠)与保持酶(充当停车位)的差异表达来实现。在折叠酶-holdase比的模型捕获变化都观察到老化过程中和生物体跨越不同的代谢率的生物体。这项工作描述了一种简单的生物物理机制,细胞蛋白变性可以通过这种机制来适应不断变化的生长环境的需求。

更新日期:2020-12-14
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