A Chemical Mutagenesis Approach to Insert Post-translational Modifications in Aggregation-Prone Proteins.
A Chemical Mutagenesis Approach to Insert Post-translational Modifications in Aggregation-Prone Proteins.
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DOI：
10.1021/acschemneuro.2c00077
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发表时间：
2022-06-15
影响因子：
5
通讯作者：
Aprile, Francesco A.
中科院分区：
文献类型：
--
作者：
Ge, Ying;Masoura, Athina;Yang, Jingzhou;Aprile, Francesco A.
神经退行性疾病是一类与神经系统中被称为淀粉样蛋白的纤维状蛋白聚集体的形成有关的病症。这种聚集过程受到多种翻译后修饰的影响，其具体机制尚未完全了解。新兴的化学诱变技术目前正在努力解决引入蛋白质翻译后修饰的挑战，同时在修饰反应期间保持蛋白质的稳定性和溶解性。几种淀粉样蛋白是高度聚集倾向，目前的修饰程序可能会导致这些蛋白质的意外沉淀，影响其产量和下游表征。在这里，我们提出了一种在化学诱变过程中保持淀粉样蛋白溶解度的方法。作为原理证明，我们应用我们的方法来模拟淀粉样β肽的40个残基长变体的丝氨酸-26的磷酸化和赖氨酸-28的乙酰化，其聚集与阿尔茨海默病有关。
Neurodegenerative diseases are a class of disorders linked to the formation in the nervous system of fibrillar protein aggregates called amyloids. This aggregation process is affected by a variety of post-translational modifications, whose specific mechanisms are not fully understood yet. Emerging chemical mutagenesis technology is currently striving to address the challenge of introducing protein post-translational modifications, while maintaining the stability and solubility of the proteins during the modification reaction. Several amyloidogenic proteins are highly aggregation-prone, and current modification procedures can lead to unexpected precipitation of these proteins, affecting their yield and downstream characterization. Here, we present a method for maintaining amyloidogenic protein solubility during chemical mutagenesis. As proof-of-principle, we applied our method to mimic the phosphorylation of serine-26 and the acetylation of lysine-28 of the 40-residue long variant of amyloid-β peptide, whose aggregation is linked to Alzheimer’s disease.
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影响因子：
5.6
作者：
Jin Y;Vadukul DM;Gialama D;Ge Y;Thrush R;White JT;Aprile FA
通讯作者：
Aprile FA
影响因子：
30.8
作者：
HENDRIKS, L;VANDUIJN, CM;VAN BROECKHOVEN, C
通讯作者：
VAN BROECKHOVEN, C
DOI：
10.1186/alzrt258
发表时间：
2014
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Kummer MP;Heneka MT
通讯作者：
Heneka MT
影响因子：
15
作者：
Rezaei-Ghaleh, Nasrollah;Amininasab, Mehriar;Zweckstetter, Markus
通讯作者：
Zweckstetter, Markus
影响因子：
25
作者：
Nilsberth, C;Westlind-Danielsson, A;Lannfelt, L
通讯作者：
Lannfelt, L