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Protein oxidation: role in signalling and detection by mass spectrometry

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Abstract

Proteins can undergo a wide variety of oxidative post-translational modifications (oxPTM); while reversible modifications are thought to be relevant in physiological processes, non-reversible oxPTM may contribute to pathological situations and disease. The oxidant is also important in determining the type of oxPTM, such as oxidation, chlorination or nitration. The best characterized oxPTMs involved in signalling modulation are partial oxidations of cysteine to disulfide, glutathionylated or sulfenic acid forms that can be reversed by thiol reductants. Proline hydroxylation in HIF signalling is also quite well characterized, and there is increasing evidence that specific oxidations of methionine and tyrosine may have some biological roles. For some proteins regulated by cysteine oxidation, the residues and molecular mechanism involved have been extensively studied and are well understood, such as the protein tyrosine phosphatase PTP1B and MAP3 kinase ASK1, as well as transcription factor complex Keap1–Nrf2. The advances in understanding of the role oxPTMs in signalling have been facilitated by advances in analytical technology, in particular tandem mass spectrometry techniques. Combinations of peptide sequencing by collisionally induced dissociation and precursor ion scanning or neutral loss to select for specific oxPTMs have proved very useful for identifying oxidatively modified proteins and mapping the sites of oxidation. The development of specific labelling and enrichment procedures for S-nitrosylation or disulfide formation has proved invaluable, and there is ongoing work to establish analogous methods for detection of nitrotyrosine and other modifications.

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Abbreviations

cICAT:

Cleavable isotope coded affinity tag

CID:

Collision induced dissociation

Duox:

Dual oxidases

ECD:

Electron capture dissociation

eNOS:

Endothelial nitric oxide synthases

ESI:

Electrospray ionization

FIH:

Factor inhibiting HIF

HIF:

Hypoxia inducible factor

iNOS:

Inducible nitric oxide synthases

iTRAQ:

Isobaric tag for relative and absolute quantification

MALDI:

Matrix assisted laser desorption/ionization

MS:

Mass spectrometry

MS/MS:

Tandem mass spectrometry

Nox:

NADPH oxidase

oxPTM:

oxidative post-translational modifications

Phox:

Phagocyte oxidase

PHD:

Proline hydroxylation domain

PTP:

Protein tyrosine phosphatase

SNO:

S-nitrosothiol

Trx:

Thioredoxin

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Authors and Affiliations

  1. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK

    Corinne M. Spickett

  2. Faculty of Biological and Life Sciences, University of Glasgow, Glasgow, UK

    Andrew R. Pitt

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  1. Corinne M. Spickett
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  2. Andrew R. Pitt
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Correspondence to Corinne M. Spickett.

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Review invited for a special issue of Amino Acids dedicated to Amino acid and protein modification by oxygen and nitrogen species.

This article is part of the Special Issue on Redoxomics of proteins and amino acids.

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Spickett, C.M., Pitt, A.R. Protein oxidation: role in signalling and detection by mass spectrometry. Amino Acids 42, 5–21 (2012). https://doi.org/10.1007/s00726-010-0585-4

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