PXD039544

PXD039544 is an original dataset announced via ProteomeXchange.

Title	N-terminal acetylome analysis reveals an expanded substrate profile for the NatC N-terminal acetyltransferase complex in yeast
Description	N-terminal acetylation is a conserved protein modification among eukaryotes, and the yeast Saccharomyces cerevisiae is a valuable model system for studying this modification. The enzymes responsible for the bulk of protein N-terminal acetylation in S. cerevisiae are the N-terminal acetyltransferases NatA, NatB and NatC. Thus far, proteome-wide identification of the in vivo protein substrates of yeast NatA and NatB has been performed by N-terminomics. Here, we used S. cerevisiae deleted for the NatC catalytic subunit Naa30 and identified 57 yeast NatC substrates by N-terminal combined fractional diagonal chromatography (COFRADIC) analysis. Interestingly, in addition to the canonical N-termini starting with ML, MI, MF and MW, yeast NatC substrates also included MY, MK, MM, MA, MV and MS. However, for some of these substrate types, such as MY, MK, MV and MS, we also uncovered (residual) non-NatC NAT activity, most likely due to the previously established redundancy between yeast NatC and NatE/Naa50. Thus, we have revealed a complex interplay between different NATs in targeting methionine-starting N-termini in yeast. Furthermore, our results showed that ectopic expression of human NAA30 rescued known NatC phenotypes in naa30∆ yeast, as well as partially restored the yeast NatC Nt-acetylome. Thus, we demonstrate an evolutionary conservation of NatC from yeast to human thereby underpinning future disease models to study pathogenic NAA30 variants. Overall, this work offers increased biochemical and functional insights into NatC-mediated N-terminal acetylation and provides a basis for future work to pinpoint the specific molecular mechanisms that link lack of NatC-mediated N-terminal acetylation to phenotypes of NatC deletion yeast
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:48:53.139.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD039544
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	An Staes
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	2xC(13),3x(2)H labeled N6-acetyl-L-lysine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-18 14:13:33	ID requested
⏵ 1	2024-10-07 13:48:54	announced

10.1016/j.jbc.2022.102824;

Van Damme P, Osberg C, Jonckheere V, Glomnes N, Gevaert K, Arnesen T, Aksnes H, vivo substrate profile of the yeast N-terminal acetyltransferase NatC. J Biol Chem, 299(2):102824(2023) [pubmed]

10.6019/PXD039544;

submitter keyword: NatC,N-terminal acetylation, N-alpha-acetyltransferase 30 (NAA30), Saccharomyces cerevisiae, N-terminal acetylome, N-terminal COFRADIC, N-terminomics.

Petra Van Damme
contact affiliation	iRIP Unit, Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, B-9000 Ghent, Belgium
contact email	Petra.VanDamme@UGent.be
lab head
An Staes
contact affiliation	Medical Protein Chemistry
contact email	an.staes@vib-ugent.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039544
     1. Label: PRIDE project
     2. Name: N-terminal acetylome analysis reveals an expanded substrate profile for the NatC N-terminal acetyltransferase complex in yeast