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Direct Proteomic Mapping of Cysteine Persulfidation.

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. Antioxid. Redox Signal. 00, 000-000.

Authors+Show Affiliations

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences • Beijing, Beijing Institute of Lifeomics, Beijing, China.State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences • Beijing, Beijing Institute of Lifeomics, Beijing, China.State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences • Beijing, Beijing Institute of Lifeomics, Beijing, China.State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences • Beijing, Beijing Institute of Lifeomics, Beijing, China.State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences • Beijing, Beijing Institute of Lifeomics, Beijing, China.State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences • Beijing, Beijing Institute of Lifeomics, Beijing, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31411056

Citation

Fu, Ling, et al. "Direct Proteomic Mapping of Cysteine Persulfidation." Antioxidants & Redox Signaling, 2019.
Fu L, Liu K, He J, et al. Direct Proteomic Mapping of Cysteine Persulfidation. Antioxid Redox Signal. 2019.
Fu, L., Liu, K., He, J., Tian, C., Yu, X., & Yang, J. (2019). Direct Proteomic Mapping of Cysteine Persulfidation. Antioxidants & Redox Signaling, doi:10.1089/ars.2019.7777.
Fu L, et al. Direct Proteomic Mapping of Cysteine Persulfidation. Antioxid Redox Signal. 2019 Sep 9; PubMed PMID: 31411056.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Direct Proteomic Mapping of Cysteine Persulfidation. AU - Fu,Ling, AU - Liu,Keke, AU - He,Jingyang, AU - Tian,Caiping, AU - Yu,Xiaobo, AU - Yang,Jing, Y1 - 2019/09/09/ PY - 2019/8/15/pubmed PY - 2019/8/15/medline PY - 2019/8/15/entrez KW - chemical proteomics KW - cysteine KW - hydrogen sulfide KW - mass spectrometry KW - persulfidation/sulfhydration KW - persulfide JF - Antioxidants & redox signaling JO - Antioxid. Redox Signal. N2 - 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. Antioxid. Redox Signal. 00, 000-000. SN - 1557-7716 UR - https://www.unboundmedicine.com/medline/citation/31411056/Direct_Proteomic_Mapping_of_Cysteine_Persulfidation_ L2 - https://www.liebertpub.com/doi/full/10.1089/ars.2019.7777?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -