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PXD017031 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLC-MS/MS analysis of immunoprecipitated NAA15-V5 variants
DescriptionThe human N-terminal acetyltransferase E (NatE) including its associated NatA co-translationally acetylates the N-terminus of about 40-60% of the proteome to mediate diverse biological processes including protein half-life, localization and protein interaction. In eukaryotes, the NatE complex contains the NAA50 catalytic subunit with substrate specificity for N-terminal methionine acetylation and NatA, which facilitates ribosomal targeting of the complex for co-translational activity. NatA, contains NAA10 catalytic and NAA15 auxiliary subunits, and forms a complex with a protein with intrinsic NAA10 inhibitory activity, HYPK. The molecular basis for how the human NAA10 and NAA50 catalytic subunits within NatE complex coordinate function and how HYPK regulates NatE activity is unknown. Here, we characterize the biochemical interplay between the human NAA10 and NAA50 catalytic subunits of NatE and its regulation by HYPK and correlate this to the cryo-EM structures of the human NatE and NatE/HYPK complexes. We show that NAA50 and HYPK exhibit negative cooperative binding to NatA in vitro and in human cells, by inducing NAA15 shifts in opposing directions. NAA50 and HYPK each contributes to NAA10 activity inhibition through structural alteration of the NAA10 substrate binding site. NatE is about 8-fold more active than NAA50, likely due to a reduced entropic cost for substrate binding through NatA tethering, but is inhibited by HYPK through structural alteration of the NatE substrate binding site. Taken together, these studies reveal the molecular basis for coordinated N-terminal acetylation by the NAA10 and NAA50 catalytic subunits of NatE and its modulation by HYPK.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNina McTiernan
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-01-09 01:38:39ID requested
12020-03-13 06:15:55announced
Publication List
Deng S, McTiernan N, Wei X, Arnesen T, Marmorstein R, Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK. Nat Commun, 11(1):818(2020) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: LC-MS/MS, N-terminal acetylation, NatE, NAA15, NAA10, NAA50, HYPK
Contact List
Thomas Arnesen
contact affiliationDepartment of Biomedicine, University of Bergen, Bergen, Norway Department of Biological Sciences, University of Bergen, Bergen, Norway Department of Surgery, Haukeland University Hospital, Bergen, Norway
contact emailthomas.arnesen@uib.no
lab head
Nina McTiernan
contact affiliationUniversity of Bergen
contact emailnina.tiernan@uib.no
dataset submitter
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