Direct Proteomic Mapping of Cysteine Persulfidation - PubMed (original) (raw)

. 2020 Nov 20;33(15):1061-1076.

doi: 10.1089/ars.2019.7777. Epub 2019 Sep 9.

Affiliations

• PMID: 31411056
• DOI: 10.1089/ars.2019.7777

Direct Proteomic Mapping of Cysteine Persulfidation

Ling Fu et al. Antioxid Redox Signal. 2020.

Abstract

Aims: Cysteine persulfidation (also called sulfhydration or sulfuration) has emerged as a potential redox mechanism to regulate protein functions and diverse biological processes in hydrogen sulfide (H2S) signaling. Due to its intrinsically unstable nature, working with this modification has proven to be challenging. Although methodological progress has expanded the inventory of persulfidated proteins, there is a continued need to develop methods that can directly and unequivocally identify persulfidated cysteine residues in complex proteomes. Results: A quantitative chemoproteomic method termed as low-pH quantitative thiol reactivity profiling (QTRP) was developed to enable direct site-specific mapping and reactivity profiling of proteomic persulfides and thiols in parallel. The method was first applied to cell lysates treated with NaHS, resulting in the identification of overall 1547 persulfidated sites on 994 proteins. Structural analysis uncovered unique consensus motifs that might define this distinct type of modification. Moreover, the method was extended to profile endogenous protein persulfides in cells expressing H2S-generating enzyme, mouse tissues, and human serum, which led to additional insights into mechanistic, structural, and functional features of persulfidation events, particularly on human serum albumin. Innovation and Conclusion: Low-pH QTRP represents the first method that enables direct and unbiased proteomic mapping of cysteine persulfidation. Our method allows to generate the most comprehensive inventory of persulfidated targets of NaHS so far and to perform the first analysis of in vivo persulfidation events, providing a valuable tool to dissect the biological functions of this important modification.

Keywords: chemical proteomics; cysteine; hydrogen sulfide; mass spectrometry; persulfidation/sulfhydration; persulfide.

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