Formation of protein cross-links by singlet oxygen-mediated disulfide oxidation

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Formation of protein cross-links by singlet oxygen-mediated disulfide oxidation. / Jiang, Shuwen; Carroll, Luke; Mariotti, Michele; Hagglund, Per; Davies, Michael J.

In: Redox Biology, Vol. 41, 101874, 2021.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Jiang, S, Carroll, L, Mariotti, M, Hagglund, P & Davies, MJ 2021, 'Formation of protein cross-links by singlet oxygen-mediated disulfide oxidation', Redox Biology, vol. 41, 101874. https://doi.org/10.1016/j.redox.2021.101874

APA

Jiang, S., Carroll, L., Mariotti, M., Hagglund, P., & Davies, M. J. (2021). Formation of protein cross-links by singlet oxygen-mediated disulfide oxidation. Redox Biology, 41, [101874]. https://doi.org/10.1016/j.redox.2021.101874

Vancouver

Jiang S, Carroll L, Mariotti M, Hagglund P, Davies MJ. Formation of protein cross-links by singlet oxygen-mediated disulfide oxidation. Redox Biology. 2021;41. 101874. https://doi.org/10.1016/j.redox.2021.101874

Author

Jiang, Shuwen ; Carroll, Luke ; Mariotti, Michele ; Hagglund, Per ; Davies, Michael J. / Formation of protein cross-links by singlet oxygen-mediated disulfide oxidation. In: Redox Biology. 2021 ; Vol. 41.

Bibtex

@article{0a7b3474206b471fbb86118362fbaf67,
title = "Formation of protein cross-links by singlet oxygen-mediated disulfide oxidation",
abstract = "Cross-links formed within and between proteins are a major cause of protein dysfunction, and are postulated to drive the accumulation of protein aggregates in some human pathologies. Cross-links can be formed from multiple residues and can be reversible (usually sulfur-sulfur bonds) or irreversible (typically carbon-carbon or carbon-heteroatom bonds). Disulfides formed from oxidation of two Cys residues are widespread, with these formed both deliberately, via enzymatic reactions, or as a result of unintended oxidation reactions. We have recently demonstrated that new protein-glutathione mixed disulfides can be formed through oxidation of a protein disulfide to a thiosulfinate, and subsequent reaction of this species with glutathione. Here we investigate whether similar reactions occur between an oxidized protein disulfide, and a Cys residues on a second protein, to give novel protein cross-links. Singlet oxygen (1O2)-mediated oxidation of multiple proteins (?-lactalbumin, lysozyme, beta-2-microglobulin, C-reactive protein), and subsequent incubation with the Cys-containing protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH), generates inter-protein cross-links as detected by SDSPAGE, immunoblotting and mass spectrometry (MS). The cross-link yield is dependent on the 1O2 concentration, the presence of the original protein disulfide bond, and the free Cys on GAPDH. MS with 18O-labeling has allowed identification of the residues involved in some cases (e.g. Cys25 from the Cys25-Cys80 disulfide in beta2-microglobulin, with Cys149 or Cys244 of GAPDH). The formation of these cross-links results in a loss of GAPDH enzymatic activity. These data provide ?proof-of-concept? for a novel mechanism of protein cross-link formation which may help rationalize the accumulation of cross-linked proteins in multiple human pathologies.",
keywords = "Disulfide, Singlet oxygen, Protein cross-links, Protein aggregation, Thiol-disulfide exchange, Post-translational modification, Photo-oxidation, INDUCED ELECTROSTATIC STABILIZATION, GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE, MOLECULAR-OXYGEN, SULFENIC ACIDS, MECHANISMS, PHOTOOXIDATION, TYROSINE, BONDS, BETA(2)-MICROGLOBULIN, INACTIVATION",
author = "Shuwen Jiang and Luke Carroll and Michele Mariotti and Per Hagglund and Davies, {Michael J.}",
year = "2021",
doi = "10.1016/j.redox.2021.101874",
language = "English",
volume = "41",
journal = "Redox Biology",
issn = "2213-2317",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Formation of protein cross-links by singlet oxygen-mediated disulfide oxidation

AU - Jiang, Shuwen

AU - Carroll, Luke

AU - Mariotti, Michele

AU - Hagglund, Per

AU - Davies, Michael J.

PY - 2021

Y1 - 2021

N2 - Cross-links formed within and between proteins are a major cause of protein dysfunction, and are postulated to drive the accumulation of protein aggregates in some human pathologies. Cross-links can be formed from multiple residues and can be reversible (usually sulfur-sulfur bonds) or irreversible (typically carbon-carbon or carbon-heteroatom bonds). Disulfides formed from oxidation of two Cys residues are widespread, with these formed both deliberately, via enzymatic reactions, or as a result of unintended oxidation reactions. We have recently demonstrated that new protein-glutathione mixed disulfides can be formed through oxidation of a protein disulfide to a thiosulfinate, and subsequent reaction of this species with glutathione. Here we investigate whether similar reactions occur between an oxidized protein disulfide, and a Cys residues on a second protein, to give novel protein cross-links. Singlet oxygen (1O2)-mediated oxidation of multiple proteins (?-lactalbumin, lysozyme, beta-2-microglobulin, C-reactive protein), and subsequent incubation with the Cys-containing protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH), generates inter-protein cross-links as detected by SDSPAGE, immunoblotting and mass spectrometry (MS). The cross-link yield is dependent on the 1O2 concentration, the presence of the original protein disulfide bond, and the free Cys on GAPDH. MS with 18O-labeling has allowed identification of the residues involved in some cases (e.g. Cys25 from the Cys25-Cys80 disulfide in beta2-microglobulin, with Cys149 or Cys244 of GAPDH). The formation of these cross-links results in a loss of GAPDH enzymatic activity. These data provide ?proof-of-concept? for a novel mechanism of protein cross-link formation which may help rationalize the accumulation of cross-linked proteins in multiple human pathologies.

AB - Cross-links formed within and between proteins are a major cause of protein dysfunction, and are postulated to drive the accumulation of protein aggregates in some human pathologies. Cross-links can be formed from multiple residues and can be reversible (usually sulfur-sulfur bonds) or irreversible (typically carbon-carbon or carbon-heteroatom bonds). Disulfides formed from oxidation of two Cys residues are widespread, with these formed both deliberately, via enzymatic reactions, or as a result of unintended oxidation reactions. We have recently demonstrated that new protein-glutathione mixed disulfides can be formed through oxidation of a protein disulfide to a thiosulfinate, and subsequent reaction of this species with glutathione. Here we investigate whether similar reactions occur between an oxidized protein disulfide, and a Cys residues on a second protein, to give novel protein cross-links. Singlet oxygen (1O2)-mediated oxidation of multiple proteins (?-lactalbumin, lysozyme, beta-2-microglobulin, C-reactive protein), and subsequent incubation with the Cys-containing protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH), generates inter-protein cross-links as detected by SDSPAGE, immunoblotting and mass spectrometry (MS). The cross-link yield is dependent on the 1O2 concentration, the presence of the original protein disulfide bond, and the free Cys on GAPDH. MS with 18O-labeling has allowed identification of the residues involved in some cases (e.g. Cys25 from the Cys25-Cys80 disulfide in beta2-microglobulin, with Cys149 or Cys244 of GAPDH). The formation of these cross-links results in a loss of GAPDH enzymatic activity. These data provide ?proof-of-concept? for a novel mechanism of protein cross-link formation which may help rationalize the accumulation of cross-linked proteins in multiple human pathologies.

KW - Disulfide

KW - Singlet oxygen

KW - Protein cross-links

KW - Protein aggregation

KW - Thiol-disulfide exchange

KW - Post-translational modification

KW - Photo-oxidation

KW - INDUCED ELECTROSTATIC STABILIZATION

KW - GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE

KW - MOLECULAR-OXYGEN

KW - SULFENIC ACIDS

KW - MECHANISMS

KW - PHOTOOXIDATION

KW - TYROSINE

KW - BONDS

KW - BETA(2)-MICROGLOBULIN

KW - INACTIVATION

U2 - 10.1016/j.redox.2021.101874

DO - 10.1016/j.redox.2021.101874

M3 - Journal article

C2 - 33601275

VL - 41

JO - Redox Biology

JF - Redox Biology

SN - 2213-2317

M1 - 101874

ER -

ID: 275432311