title: Site-specific mapping and time-resolved monitoring of lysine methylation by high-resolution NMR spectroscopy.
abstract: Methylation and acetylation of protein lysine residues constitute abundant post-translational modifications (PTMs) that regulate a plethora of biological processes. In eukaryotic proteins, lysines are often mono-, di-, or trimethylated, which may signal different biological outcomes. Deconvoluting these different PTM types and PTM states is not easily accomplished with existing analytical tools. Here, we demonstrate the unique ability of NMR spectroscopy to discriminate between lysine acetylation and mono-, di-, or trimethylation in a site-specific and quantitative manner. This enables mapping and monitoring of lysine acetylation and methylation reactions in a nondisruptive and continuous fashion. Time-resolved NMR measurements of different methylation events in complex environments including cell extracts contribute to our understanding of how these PTMs are established in vitro and in vivo.
authors.affiliation: Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert Roessle Strasse 10, 13125 Berlin, Germany.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Theillet
authors.forename: Stamatios
authors.initials: S
authors.lastname: Liokatis
authors.forename: Jan Oliver
authors.initials: JO
authors.lastname: Jost
authors.forename: Beata
authors.initials: B
authors.lastname: Bekei
authors.forename: Honor May
authors.initials: HM
authors.lastname: Rose
authors.forename: Andres
authors.initials: A
authors.lastname: Binolfi
authors.forename: Dirk
authors.initials: D
authors.lastname: Schwarzer
authors.forename: Philipp
authors.initials: P
authors.lastname: Selenko
mesh_terms: D000107:Acetylation; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000032:analysis / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine