title: Redox proteomics of protein-bound methionine oxidation.
abstract: We here present a new method to measure the degree of protein-bound methionine sulfoxide formation at a proteome-wide scale. In human Jurkat cells that were stressed with hydrogen peroxide, over 2000 oxidation-sensitive methionines in more than 1600 different proteins were mapped and their extent of oxidation was quantified. Meta-analysis of the sequences surrounding the oxidized methionine residues revealed a high preference for neighboring polar residues. Using synthetic methionine sulfoxide containing peptides designed according to the observed sequence preferences in the oxidized Jurkat proteome, we discovered that the substrate specificity of the cellular methionine sulfoxide reductases is a major determinant for the steady-state of methionine oxidation. This was supported by a structural modeling of the MsrA catalytic center. Finally, we applied our method onto a serum proteome from a mouse sepsis model and identified 35 in vivo methionine oxidation events in 27 different proteins.
authors.affiliation: Department of Medical Protein Research, VIB, B-9000 Ghent, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Ghesquière
authors.forename: Veronique
authors.initials: V
authors.lastname: Jonckheere
authors.forename: Niklaas
authors.initials: N
authors.lastname: Colaert
authors.forename: Joost
authors.initials: J
authors.lastname: Van Durme
authors.forename: Evy
authors.initials: E
authors.lastname: Timmerman
authors.forename: Marc
authors.initials: M
authors.lastname: Goethals
authors.forename: Joost
authors.initials: J
authors.lastname: Schymkowitz
authors.forename: Frederic
authors.initials: F
authors.lastname: Rousseau
authors.forename: Joël
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: Kris
authors.initials: K
authors.lastname: Gevaert
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D020134:Catalytic Domain; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019169:Jurkat Cells; D015201:Meta-Analysis as Topic; D008715:Methionine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000737:chemistry; D020543:Proteome / Q000737:chemistry* / Q000378:metabolism; D012480:Salmonella Infections / Q000097:blood; D012477:Salmonella enteritidis; D012772:Shock, Septic / Q000097:blood
chemical_list: D016877:Oxidants; D020543:Proteome; D008715:Methionine; D006861:Hydrogen Peroxide; D050862:Oxidoreductases Acting on Sulfur Group Donors; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; C524352:MSRB3 protein, human; C013111:methionine sulfoxide