title: Protein N-terminal acetyltransferases act as N-terminal propionyltransferases in vitro and in vivo.
abstract: N-terminal acetylation (Nt-acetylation) is a highly abundant protein modification in eukaryotes catalyzed by N-terminal acetyltransferases (NATs), which transfer an acetyl group from acetyl coenzyme A to the alpha amino group of a nascent polypeptide. Nt-acetylation has emerged as an important protein modifier, steering protein degradation, protein complex formation and protein localization. Very recently, it was reported that some human proteins could carry a propionyl group at their N-terminus. Here, we investigated the generality of N-terminal propionylation by analyzing its proteome-wide occurrence in yeast and we identified 10 unique in vivo Nt-propionylated N-termini. Furthermore, by performing differential N-terminome analysis of a control yeast strain (yNatA), a yeast NatA deletion strain (yNatAΔ) or a yeast NatA deletion strain expressing human NatA (hNatA), we were able to demonstrate that in vivo Nt-propionylation of several proteins, displaying a NatA type substrate specificity profile, depended on the presence of either yeast or human NatA. Furthermore, in vitro Nt-propionylation assays using synthetic peptides, propionyl coenzyme A, and either purified human NATs or immunoprecipitated human NatA, clearly demonstrated that NATs are Nt-propionyltransferases (NPTs) per se. We here demonstrate for the first time that Nt-propionylation can occur in yeast and thus is an evolutionarily conserved process, and that the NATs are multifunctional enzymes acting as NPTs in vivo and in vitro, in addition to their main role as NATs, and their potential function as lysine acetyltransferases (KATs) and noncatalytic regulators.
authors.affiliation: Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway.
authors.forename: Håvard
authors.initials: H
authors.lastname: Foyn
authors.forename: Petra
authors.initials: P
authors.lastname: Van Damme
authors.forename: Svein I
authors.initials: SI
authors.lastname: Støve
authors.forename: Nina
authors.initials: N
authors.lastname: Glomnes
authors.forename: Rune
authors.initials: R
authors.lastname: Evjenth
authors.forename: Kris
authors.initials: K
authors.lastname: Gevaert
authors.forename: Thomas
authors.initials: T
authors.lastname: Arnesen
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008239:Lysine / Q000378:metabolism; D063206:N-Terminal Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D020543:Proteome; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D000596:Amino Acids; D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; C539688:NatA protein, S cerevisiae; D063206:N-Terminal Acetyltransferases; D008239:Lysine