title: The N-terminal Acetyltransferase Naa10/ARD1 Does Not Acetylate Lysine Residues.
abstract: The N-terminal acetyltransferase NatA is a heterodimeric complex consisting of a catalytic subunit (Naa10/ARD1) and an auxiliary subunit (Naa15). NatA co-translationally acetylates the N termini of a wide variety of nascent polypeptides. In addition, Naa10 can act independently to posttranslationally acetylate a distinct set of substrates, notably actin. Recent structural studies of Naa10 have also revealed the molecular basis for N-terminal acetylation specificity. Surprisingly, recent reports claim that Naa10 may also acetylate lysine residues of diverse targets, including methionine sulfoxide reductase A, myosin light chain kinase, and Runt-related transcription factor 2. Here we used recombinant proteins to reconstitute and assess lysine acetylation events catalyzed by Naa10 in vitro. We show that there is no difference in lysine acetylation of substrate proteins with or without Naa10, suggesting that the substrates may be acetylated chemically rather than enzymatically. Together, our data argue against a role for Naa10 in lysine acetylation.
authors.affiliation: From the Department of Biochemistry and Biophysics, Abramson Family Cancer Research Institute, and Graduate Group in Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Magin
authors.affiliation: From the Department of Biochemistry and Biophysics, Graduate Group in Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: March
authors.affiliation: From the Department of Biochemistry and Biophysics, Abramson Family Cancer Research Institute, and the Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 marmor@mail.med.upenn.edu.
authors.forename: Ronen
authors.initials: R
authors.lastname: Marmorstein
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D063209:N-Terminal Acetyltransferase A / Q000378:metabolism*; D063213:N-Terminal Acetyltransferase E / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D063209:N-Terminal Acetyltransferase A; C504824:NAA10 protein, human; D063213:N-Terminal Acetyltransferase E; D009219:Myosin-Light-Chain Kinase; D008239:Lysine
keywords: ARD1; NAT; Naa10p; acetyl-CoA; acetylation; acetyltransferase; chemical acetylation; posttranslational modification (PTM); transcription factor