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Proteomics. 2019 Mar;19(6):e1800070. doi: 10.1002/pmic.201800070. Epub 2019 Jan 28.

Large-Scale Analysis of Redox-Sensitive Conditionally Disordered Protein Regions Reveals Their Widespread Nature and Key Roles in High-Level Eukaryotic Processes.

Author information

1
MTA-ELTE Lendület Bioinformatics Research Group, Department of Biochemistry, Eötvös Loránd University, Budapest, H-1117, Hungary.
2
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, 69117, Germany.
3
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.

Abstract

Recently developed quantitative redox proteomic studies enable the direct identification of redox-sensing cysteine residues that regulate the functional behavior of target proteins in response to changing levels of reactive oxygen species. At the molecular level, redox regulation can directly modify the active sites of enzymes, although a growing number of examples indicate the importance of an additional underlying mechanism that involves conditionally disordered proteins. These proteins alter their functional behavior by undergoing a disorder-to-order transition in response to changing redox conditions. However, the extent to which this mechanism is used in various proteomes is currently unknown. Here, a recently developed sequence-based prediction tool incorporated into the IUPred2A web server is used to estimate redox-sensitive conditionally disordered regions at a large scale. It is shown that redox-sensitive conditional disorder is fairly widespread in various proteomes and that its presence strongly correlates with the expansion of specific domains in multicellular organisms that largely rely on extra stability provided by disulfide bonds or zinc ion binding. The analyses of yeast redox proteomes and human disease data further underlie the significance of this phenomenon in the regulation of a wide range of biological processes, as well as its biomedical importance.

KEYWORDS:

conditional disorder; intrinsically disordered proteins; redox proteomics; redox-sensitive structural switches; thiol switches

PMID:
30628183
DOI:
10.1002/pmic.201800070

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