The Human 2-Cys Peroxiredoxins form Widespread, Cysteine-Dependent- and Isoform-Specific Protein-Protein Interactions
Redox signaling is controlled by the reversible oxidation of cysteine thiols, a post-translational modification triggered by H<sub>2</sub>O<sub>2</sub> acting as a second messenger. However, H<sub>2</sub>O<sub>2</sub> actually reacts poorly with most c...
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| Main Authors: | , , , , , , |
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| Format: | Book |
| Published: |
MDPI AG,
2021-04-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | Redox signaling is controlled by the reversible oxidation of cysteine thiols, a post-translational modification triggered by H<sub>2</sub>O<sub>2</sub> acting as a second messenger. However, H<sub>2</sub>O<sub>2</sub> actually reacts poorly with most cysteine thiols and it is not clear how H<sub>2</sub>O<sub>2</sub> discriminates between cysteines to trigger appropriate signaling cascades in the presence of dedicated H<sub>2</sub>O<sub>2</sub> scavengers like peroxiredoxins (PRDXs). It was recently suggested that peroxiredoxins act as peroxidases and facilitate H<sub>2</sub>O<sub>2</sub>-dependent oxidation of redox-regulated proteins via disulfide exchange reactions. It is unknown how the peroxiredoxin-based relay model achieves the selective substrate targeting required for adequate cellular signaling. Using a systematic mass-spectrometry-based approach to identify cysteine-dependent interactors of the five human 2-Cys peroxiredoxins, we show that all five human 2-Cys peroxiredoxins can form disulfide-dependent heterodimers with a large set of proteins. Each isoform displays a preference for a subset of disulfide-dependent binding partners, and we explore isoform-specific properties that might underlie this preference. We provide evidence that peroxiredoxin-based redox relays can proceed via two distinct molecular mechanisms. Altogether, our results support the theory that peroxiredoxins could play a role in providing not only reactivity but also selectivity in the transduction of peroxide signals to generate complex cellular signaling responses. |
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| Item Description: | 10.3390/antiox10040627 2076-3921 |