Accessible Requires Authentication Published by De Gruyter January 10, 2015

Enzymatic control of cysteinyl thiol switches in proteins

Marcel Deponte and Christopher Horst Lillig
From the journal Biological Chemistry


The spatiotemporal modification of specific cysteinyl residues in proteins has emerged as a novel concept in signal transduction. Such modifications alter the redox state of the cysteinyl thiol group, with implications for the structure and biological function of the protein. Regulatory cysteines are therefore classified as ‘thiol switches’. In this review we emphasize the relevance of enzymes for specific and efficient redox sensing, evaluate prerequisites and general properties of redox switches, and highlight mechanistic principles for toggling thiol switches. Moreover, we provide an overview of potential mechanisms for the initial formation of regulatory disulfide bonds. In brief, we address the three basic questions (i) what defines a thiol switch, (ii) which parameters confer signal specificity, and (iii) how are thiol switches oxidized?

Corresponding authors: Marcel Deponte, Department of Parasitology, Ruprecht Karls University, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany, e-mail: ; and Christopher Horst Lillig, Institute for Medical Biochemistry and Molecular Biology, University Medicine, Ernst Moritz Arndt University, Ferdinand-Sauerbruch-Strasse, D-17475 Greifswald, Germany, e-mail:


This work was supported by the Deutsche Forschungsgemeinschaft (DFG grants DE 1431/8–1 to M.D. and LI 984/3–1 to C.H.L.) in the frame of the Priority Programme ‘Dynamics of Thiol-based Redox Switches in Cellular Physiology’ (SPP 1710).


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Received: 2014-11-28
Accepted: 2014-12-23
Published Online: 2015-1-10
Published in Print: 2015-5-1

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