Mapping Native Disulfide Bonds at a Proteome Scale

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2015 Feb 10

PMID 25664544

Citations 59

Authors

Shan Lu

Sheng-Bo Fan

Bing Yang

Yu-Xin Li

Jia-Ming Meng

Long Wu

Pin Li

Kun Zhang

Mei-Jun Zhang

Yan Fu

Jincai Luo

Rui-Xiang Sun

Si-Min He

Meng-Qiu Dong

Affiliations

Soon will be listed here.

Abstract

We developed a high-throughput mass spectrometry method, pLink-SS (http://pfind.ict.ac.cn/software/pLink/2014/pLink-SS.html), for precise identification of disulfide-linked peptides. Using pLink-SS, we mapped all native disulfide bonds of a monoclonal antibody and ten standard proteins. We performed disulfide proteome analyses and identified 199 disulfide bonds in Escherichia coli and 568 in proteins secreted by human endothelial cells. We discovered many regulatory disulfide bonds involving catalytic or metal-binding cysteine residues.

Citing Articles

Structural basis for the asymmetric binding of coactivator SRC1 to FXR-RXRα and allosteric communication within the complex.

Sheng Y, Guo Y, Zhao B, Sun M, Dong Y, Yin Y Commun Biol. 2025; 8(1):425.

PMID: 40082595 PMC: 11906777. DOI: 10.1038/s42003-025-07854-x.

In vitro reconstitution of meiotic DNA double-strand-break formation.

Tang X, Hu Z, Ding J, Wu M, Guan P, Song Y Nature. 2025; .

PMID: 39972125 DOI: 10.1038/s41586-024-08551-1.

Copper-dependent halogenase catalyses unactivated C-H bond functionalization.

Chiang C, Ohashi M, Le J, Chen P, Zhou Q, Qu S Nature. 2025; 638(8049):126-132.

PMID: 39880944 DOI: 10.1038/s41586-024-08362-4.

O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation.

Gou J, Bi J, Wang K, Lei L, Feng Y, Tan Z Cell Commun Signal. 2025; 23(1):43.

PMID: 39849461 PMC: 11761745. DOI: 10.1186/s12964-025-02058-6.

A versatile entry to unnatural, disulfide-linked amino acids and peptides through the disulfuration of azlactones.

Iwata M, Takami Y, Asanuma H, Hosono K, Ohno H, Yoshikai N Chem Sci. 2025; 16(6):2777-2784.

PMID: 39810996 PMC: 11726236. DOI: 10.1039/d4sc07187e.

References

van der Veen A, Ploegh H . Ubiquitin-like proteins. Annu Rev Biochem. 2012; 81:323-57. DOI: 10.1146/annurev-biochem-093010-153308. View

Nossal N, HEPPEL L . The release of enzymes by osmotic shock from Escherichia coli in exponential phase. J Biol Chem. 1966; 241(13):3055-62. View

Wu S, Jiang H, Lu Q, Dai S, Hancock W, Karger B . Mass spectrometric determination of disulfide linkages in recombinant therapeutic proteins using online LC-MS with electron-transfer dissociation. Anal Chem. 2009; 81(1):112-22. PMC: 2645030. DOI: 10.1021/ac801560k. View

Cook K, Hogg P . Post-translational control of protein function by disulfide bond cleavage. Antioxid Redox Signal. 2012; 18(15):1987-2015. DOI: 10.1089/ars.2012.4807. View

Vertommen D, Depuydt M, Pan J, Leverrier P, Knoops L, Szikora J . The disulphide isomerase DsbC cooperates with the oxidase DsbA in a DsbD-independent manner. Mol Microbiol. 2007; 67(2):336-49. PMC: 2614554. DOI: 10.1111/j.1365-2958.2007.06030.x. View

Smoot M, Ono K, Ruscheinski J, Wang P, Ideker T . Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2010; 27(3):431-2. PMC: 3031041. DOI: 10.1093/bioinformatics/btq675. View

Xu H, Zhang L, Freitas M . Identification and characterization of disulfide bonds in proteins and peptides from tandem MS data by use of the MassMatrix MS/MS search engine. J Proteome Res. 2007; 7(1):138-44. PMC: 2749473. DOI: 10.1021/pr070363z. View

Depuydt M, Messens J, Collet J . How proteins form disulfide bonds. Antioxid Redox Signal. 2010; 15(1):49-66. DOI: 10.1089/ars.2010.3575. View

Gotze M, Pettelkau J, Schaks S, Bosse K, Ihling C, Krauth F . StavroX--a software for analyzing crosslinked products in protein interaction studies. J Am Soc Mass Spectrom. 2011; 23(1):76-87. DOI: 10.1007/s13361-011-0261-2. View

10.

Hilgers M, Ludwig M . Crystal structure of the quorum-sensing protein LuxS reveals a catalytic metal site. Proc Natl Acad Sci U S A. 2001; 98(20):11169-74. PMC: 58702. DOI: 10.1073/pnas.191223098. View

11.

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A . ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009; 25(8):1091-3. PMC: 2666812. DOI: 10.1093/bioinformatics/btp101. View

12.

Monnier V, Mustata G, Biemel K, Reihl O, Lederer M, Zhenyu D . Cross-linking of the extracellular matrix by the maillard reaction in aging and diabetes: an update on "a puzzle nearing resolution". Ann N Y Acad Sci. 2005; 1043:533-44. DOI: 10.1196/annals.1333.061. View

13.

Bader G, Hogue C . An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics. 2003; 4:2. PMC: 149346. DOI: 10.1186/1471-2105-4-2. View

14.

Hogg P . Disulfide bonds as switches for protein function. Trends Biochem Sci. 2003; 28(4):210-4. DOI: 10.1016/S0968-0004(03)00057-4. View

15.

Kadokura H, Tian H, Zander T, Bardwell J, Beckwith J . Snapshots of DsbA in action: detection of proteins in the process of oxidative folding. Science. 2004; 303(5657):534-7. DOI: 10.1126/science.1091724. View

16.

Zhu J, Knottenbelt S, Kirk M, Pei D . Catalytic mechanism of S-ribosylhomocysteinase: ionization state of active-site residues. Biochemistry. 2006; 45(40):12195-203. DOI: 10.1021/bi061434v. View

17.

Tabb D, McDonald W, Yates 3rd J . DTASelect and Contrast: tools for assembling and comparing protein identifications from shotgun proteomics. J Proteome Res. 2003; 1(1):21-6. PMC: 2811961. DOI: 10.1021/pr015504q. View

18.

OShea J, Chou M, Quader S, Ryan J, Church G, Schwartz D . pLogo: a probabilistic approach to visualizing sequence motifs. Nat Methods. 2013; 10(12):1211-2. DOI: 10.1038/nmeth.2646. View

19.

Bassler B, Wright M, Silverman M . Multiple signalling systems controlling expression of luminescence in Vibrio harveyi: sequence and function of genes encoding a second sensory pathway. Mol Microbiol. 1994; 13(2):273-86. DOI: 10.1111/j.1365-2958.1994.tb00422.x. View

20.

Zhang W, Marzilli L, Rouse J, Czupryn M . Complete disulfide bond assignment of a recombinant immunoglobulin G4 monoclonal antibody. Anal Biochem. 2002; 311(1):1-9. DOI: 10.1016/s0003-2697(02)00394-9. View