Total chemical synthesis of ester-linked ubiquitinated proteins unravels their behavior with deubiquitinases†,Chemical Science

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Total chemical synthesis of ester-linked ubiquitinated proteins unravels their behavior with deubiquitinases†
Chemical Science ( IF 7.6 ) Pub Date : 2018-01-11 00:00:00 , DOI: 10.1039/c7sc04518b
Hao Sun ₁ , Roman Meledin ₁ , Sachitanand M Mali ₁ , Ashraf Brik ₁

Affiliation

Ester-linked ubiquitinated proteins have been reported by several groups to be involved in ubiquitin signalling. However, due to the lack of the suitable tools to homogeneously produce such conjugates, their exact physiological roles and biochemical behavior remain enigmatic. Here, we report for the first time on the development of a novel synthetic strategy based on total chemical synthesis of proteins to construct ubiquitinated proteins, where ubiquitin is linked to the substrate via an ester bond. In this study, we prepared ester- and isopeptide-linked ubiquitinated α-globin and examined their relative behaviors with various deubiquitinases. We found that deubiquitinases are able to cleave the ester linkage with different efficiency relative to the isopeptide-linked substrate. These results may indicate that ester-linked ubiquitinated proteins are natural substrates for deubiquitinases.

中文翻译：

酯连接的泛素化蛋白的全化学合成揭示了它们与去泛素化酶的行为†

多个研究小组已报道酯连接的泛素化蛋白参与泛素信号传导。然而，由于缺乏均匀生产此类缀合物的合适工具，它们的确切生理作用和生化行为仍然是个谜。在这里，我们首次报告了一种基于蛋白质全化学合成的新型合成策略的开发，以构建泛素化蛋白质，其中泛素通过酯键与底物连接。在这项研究中，我们制备了酯连接和异肽连接的泛素化 α-珠蛋白，并检查了它们与各种去泛素酶的相关行为。我们发现，相对于异肽连接的底物，去泛素酶能够以不同的效率裂解酯键。这些结果可能表明酯连接的泛素化蛋白是去泛素酶的天然底物。

更新日期：2018-01-11

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