Dataset Information

Chaetomium thermophilum Naa50 and Naa15 TMT-labeled LC-MSMS

ABSTRACT: TMT-labeled LC-MSMS was performed to identify and quantify proteins from three different TAP-purification pull-outs from Chaetomium thermophilum. The aim was to identify interaction partners and to study, whether the two tagged proteins (Naa50 and Naa15) are likely to interact, as they do in other organisms. CtNaa50 is a special homolog of known Naa50 proteins and in this case, it does not interact with Naa15, but other identified proteins.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Chaetomium Thermophilum (strain Dsm 1495 / Cbs 144.50 / Imi 039719)

SUBMITTER: Jonas Weidenhausen

LAB HEAD: Irmgard Sinning

PROVIDER: PXD035320 | Pride | 2022-10-14

REPOSITORIES: Pride

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Publications

Extended N-Terminal Acetyltransferase Naa50 in Filamentous Fungi Adds to Naa50 Diversity.

Weidenhausen Jonas J Kopp Jürgen J Ruger-Herreros Carmen C Stein Frank F Haberkant Per P Lapouge Karine K Sinning Irmgard I

International journal of molecular sciences 20220916 18

Most eukaryotic proteins are N-terminally acetylated by a set of Nα acetyltransferases (NATs). This ancient and ubiquitous modification plays a fundamental role in protein homeostasis, while mutations are linked to human diseases and phenotypic defects. In particular, Naa50 features species-specific differences, as it is inactive in yeast but active in higher eukaryotes. Together with NatA, it engages in NatE complex formation for cotranslational acetylation. Here, we report Naa50 homologs from ...[more]

PMID: 36142717

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Project description:Rationale- NAA15 is a component of the N-terminal (Nt) acetyltransferase complex, NatA. The mechanism by which NAA15 haploinsufficiency causes congenital heart disease (CHD) remains unknown. To better understand molecular processes by which NAA15 haploinsufficiency perturbs cardiac development, we introduced NAA15 variants into human induced pluripotent stem cells (iPSCs) and assessed the consequences of these mutations on RNA and protein expression. Objective- We aim to understand the role of NAA15 haploinsufficiency in cardiac development by investigating proteomic effects on NatA complex activity, and identifying proteins dependent upon a full amount of NAA15.Methods and Results - We introduced heterozygous LoF, compound heterozygous and missense residues (R276W) in iPS cells using CRISPR/Cas9. Haploinsufficient NAA15 iPS cells differentiate into cardiomyocytes, unlike NAA15-null iPS cells, presumably due to altered composition of NatA. Mass spectrometry (MS) analyses reveal ~80% of identified iPS cell NatA targeted proteins displayed partial or complete Nt-acetylation. Between null and haploinsufficient NAA15 cells Nt-acetylation levels of 32 and 9 NatA-specific targeted proteins were reduced, respectively. Similar acetylation loss in few proteins occurred in NAA15 R276W iPSCs. In addition, steady-state protein levels of 562 proteins were altered in both null and haploinsufficient NAA15 cells; eighteen were ribosomal-associated proteins. At least four proteins were encoded by genes known to cause autosomal dominant CHD. Conclusions - These studies define a set of human proteins that requires a full NAA15 complement for normal synthesis and development. A 50% reduction in the amount of NAA15 alters levels of at least 562 proteins and Nt-acetylation of only 9 proteins. One or more modulated proteins are likely responsible for NAA15-haploinsufficiency mediated CHD. Additionally, genetically engineered iPS cells provide a platform for evaluating the consequences of amino acid sequence variants of unknown significance on NAA15 function.

Dataset Information

Chaetomium thermophilum Naa50 and Naa15 TMT-labeled LC-MSMS

Publications

Extended N-Terminal Acetyltransferase Naa50 in Filamentous Fungi Adds to Naa50 Diversity.

Similar Datasets

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