Issue 6, 2018

Total chemical synthesis of ester-linked ubiquitinated proteins unravels their behavior with deubiquitinases

Abstract

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.

Graphical abstract: Total chemical synthesis of ester-linked ubiquitinated proteins unravels their behavior with deubiquitinases

Supplementary files

Article information

Article type
Edge Article
Submitted
18 Oct 2017
Accepted
19 Dec 2017
First published
11 Jan 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2018,9, 1661-1665

Total chemical synthesis of ester-linked ubiquitinated proteins unravels their behavior with deubiquitinases

H. Sun, R. Meledin, Sachitanand M. Mali and A. Brik, Chem. Sci., 2018, 9, 1661 DOI: 10.1039/C7SC04518B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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