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The Human N-Alpha-Acetyltransferase 40 (hNaa40p/ hNatD) Is Conserved from Yeast and N-Terminally Acetylates Histones H2A and H4

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dc.contributor.author Hole, Kristine
dc.contributor.author Van Damme, Petra
dc.contributor.author Dalva, Monica
dc.contributor.author Aksnes, Henriette
dc.contributor.author Glomnes, Nina
dc.contributor.author Varhaug, Jan Erik
dc.contributor.author Lillehaug, Johan
dc.contributor.author Gevaert, Kris
dc.contributor.author Arnesen, Thomas
dc.date.accessioned 2012-02-20T11:49:42Z
dc.date.available 2012-02-20T11:49:42Z
dc.date.issued 2011-09-15
dc.identifier.citation PLoS ONE 6(9): e24713 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0024713
dc.identifier.uri http://hdl.handle.net/1956/5622
dc.description.abstract Protein Na-terminal acetylation (Nt-acetylation) is considered one of the most common protein modification in eukaryotes, and 80-90% of all soluble human proteins are modified in this way, with functional implications ranging from altered protein function and stability to translocation potency amongst others. Nt-acetylation is catalyzed by N-terminal acetyltransferases (NATs), and in yeast five NAT types are identified and denoted NatA-NatE. Higher eukaryotes additionally express NatF. Except for NatD, human orthologues for all yeast NATs are identified. yNatD is defined as the catalytic unit Naa40p (Nat4) which co-translationally Nt-acetylates histones H2A and H4. In this study we identified and characterized hNaa40p/hNatD, the human orthologue of the yeast Naa40p. An in vitro proteome-derived peptide library Nt-acetylation assay indicated that recombinant hNaa40p acetylates N-termini starting with the consensus sequence Ser-Gly-Gly-Gly-Lys-, strongly resembling the N-termini of the human histones H2A and H4. This was confirmed as recombinant hNaa40p Nt-acetylated the oligopeptides derived from the N-termini of both histones. In contrast, a synthetically Nt-acetylated H4 N-terminal peptide with all lysines being non-acetylated, was not significantly acetylated by hNaa40p, indicating that hNaa40p catalyzed H4 Na- acetylation and not H4 lysine Ne-acetylation. Also, immunoprecipitated hNaa40p specifically Nt-acetylated H4 in vitro. Heterologous expression of hNaa40p in a yeast naa40-D strain restored Nt-acetylation of yeast histone H4, but not H2A in vivo, probably reflecting the fact that the N-terminal sequences of human H2A and H4 are highly similar to each other and to yeast H4 while the N-terminal sequence of yeast H2A differs. Thus, Naa40p seems to have co-evolved with the human H2A sequence. Finally, a partial co-sedimentation with ribosomes indicates that hNaa40p co-translationally acetylates H2A and H4. Combined, our results strongly suggest that human Naa40p/NatD is conserved from yeast. Thus, the NATs of all classes of N-terminally acetylated proteins in humans now appear to be accounted for. en
dc.language.iso eng en
dc.publisher Public Library of Science en
dc.rights Copyright 2011 Hole et al. en
dc.rights.uri http://creativecommons.org/licenses/by/2.5/ en
dc.title The Human N-Alpha-Acetyltransferase 40 (hNaa40p/ hNatD) Is Conserved from Yeast and N-Terminally Acetylates Histones H2A and H4 en
dc.type Peer reviewed en
dc.type Journal article en
dc.subject.nsi VDP::Mathematics and natural science: 400::Basic biosciences: 470 en
dc.subject.nsi VDP::Medical disciplines: 700::Clinical medical disciplines: 750 en
dc.type.version publishedVersion en


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