title: Thiol-based redox signalling: rust never sleeps.
abstract: Cysteine residues in proteins are covalently modified under conditions of oxidative and nitrosative stress by oxidation, nitrosation, glutathionylation and disulfide formation. Modifications induce conformational changes in substrate proteins, effecting signal cascades that evoke a biological response. A growing number of structures with modified cysteines are allowing a piecemeal understanding of the mechanistic aspects of these signalling pathways to emerge. Conformational changes upon conjugation of nitric oxide and glutathione are generally small and often accompanied by a local increase in protein disorder. Burial of nitric oxide is also apparent, which may increase the timeframe of signalling. Conformational changes upon disulfide formation/reduction range from the small to the spectacular. They include order/disorder transitions; oxidation of disulfides following expulsion of metals such as Zn; major reorganisation or "morphing" of portions of the polypeptide backbone; and changes in quaternary structure including domain swapping.
authors.affiliation: Deakin University, Geelong 3217, Vic, Australia. m.wouters@deakin.edu.au
authors.forename: Merridee A
authors.initials: MA
authors.lastname: Wouters
authors.forename: Siiri
authors.initials: S
authors.lastname: Iismaa
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Fan
authors.forename: Naomi L
authors.initials: NL
authors.lastname: Haworth
mesh_terms: D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004220:Disulfides; D011506:Proteins; D017382:Reactive Oxygen Species; D005978:Glutathione; D003545:Cysteine