Accessible Requires Authentication Published by De Gruyter February 25, 2015

Incidence and physiological relevance of protein thiol switches

Lars I. Leichert and Tobias P. Dick
From the journal Biological Chemistry


A few small-molecule oxidants, most notably hydrogen peroxide, can act as messengers in signal transduction. They trigger so-called ‘thiol switches’, cysteine residues that are reversibly oxidized to transiently change the functional properties of their host proteins. The proteome-wide identification of functionally relevant ‘thiol switches’ is of significant interest. Unfortunately, prediction of redox-active cysteine residues on the basis of surface accessibility and other computational parameters appears to be of limited use. Proteomic thiol labeling approaches remain the most reliable strategy to discover new thiol switches in a hypothesis-free manner. We discuss if and how genomic knock-in strategies can help establish the physiological relevance of a ‘thiol switch’ on the organismal level. We conclude that surprisingly few attempts have been made to thoroughly verify the physiological relevance of thiol-based redox switches in mammalian model organisms.

Corresponding authors: Lars I. Leichert, Ruhr-Universität Bochum, Institute of Biochemistry and Pathobiochemistry – Microbial Biochemistry, Universitätsstr. 150, D-44780 Bochum, Germany, e-mail: ; and Tobias P. Dick, Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany, e-mail:


We thank Bruce Morgan for his critical comments regarding the manuscript. We would like to acknowledge funding from the Deutsche Forschungsgemeinschaft under the priority program SPP 1710 (DFG Grants LE 2905/1-1 to L.I.L. and DI 731/3-1 to T.P.D.)


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Received: 2014-12-14
Accepted: 2015-2-21
Published Online: 2015-2-25
Published in Print: 2015-5-1

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