Protein oxidation: role in signalling and detection by mass spectrometry

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pages5-21
Number of pages17
JournalAmino Acids
Volume42
Issue number1
DOIs
Publication statusPublished - Jan 2012

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Post Translational Protein Processing
Mass spectrometry
Mass Spectrometry
Disulfides
Oxidation
Cysteine
Sulfenic Acids
Physiological Phenomena
MAP Kinase Kinase Kinases
Proteins
Protein Tyrosine Phosphatases
Halogenation
Reducing Agents
Hydroxylation
Tandem Mass Spectrometry
Sulfhydryl Compounds
Proline
Oxidants
Methionine
Tyrosine

Keywords

  • redox signalling
  • nitrotyrosine
  • oxidative stress
  • precursor ion scanning
  • cysteine oxidation

Cite this

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Protein oxidation : role in signalling and detection by mass spectrometry. / Spickett, Corinne M; Pitt, Andrew R.

In: Amino Acids, Vol. 42, No. 1, 01.2012, p. 5-21.

Research output: Contribution to journalArticle

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