Consequences of post-translational modifications on amyloid proteins as revealed by protein semisynthesis.

Consequences of post-translational modifications on amyloid proteins as revealed by protein semisynthesis.
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DOI:
10.1016/j.cbpa.2021.05.007
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发表时间:
2021-10
影响因子:
7.8
通讯作者:
Pratt MR
Pratt MR
中科院分区:
生物学2区
文献类型:
--
作者:
Moon SP;Balana AT;Pratt MR

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某些类型的翻译后修饰(PTM)的整体水平的改变通常在神经退行性疾病中观察到。这些PTM变化对这些疾病进展的净影响可以从细胞和动物研究中推断出来。然而,在分子水平上,一个PTM如何影响给定的蛋白质是不统一的,不能很容易地从系统观察中概括出来,因此需要蛋白质特异性的询问。鉴于蛋白质聚集是神经变性的共同病理标志,了解这些PTM如何影响淀粉样蛋白形成蛋白的行为是很重要的。为此目的,蛋白质半合成技术,主要是通过天然化学和表达的蛋白质连接,已被广泛使用。迄今为止,这些方法已经使我们增加了对某些PTM对淀粉样蛋白的内源性功能的位点特异性后果、它们的聚集倾向以及这些PTM对形成的聚集体诱导的结构变化的理解。
Alterations to the global levels of certain types of post-translational modifications (PTMs) are commonly observed in neurodegenerative diseases. The net influence of these PTM changes to the progression of these diseases can be deduced from cellular and animal studies. However, at the molecular level, how one PTM influences a given protein is not uniform and cannot be easily generalized from systemic observations, thus requiring protein-specific interrogations. Given that protein aggregation is a shared pathological hallmark in neurodegeneration, it is important to understand how these PTMs affect the behavior of amyloid-forming proteins. For this purpose, protein semi-synthesis techniques, largely via native chemical and expressed protein ligation, have been widely used. These approaches have thus far led to our increased understanding of the site-specific consequences of certain PTMs to amyloidogenic proteins’ endogenous function, their propensity for aggregation, and the structural variations these PTMs induce towards the aggregates formed.
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