دورية أكاديمية
Expanded in vivo substrate profile of the yeast N-terminal acetyltransferase NatC.
| العنوان: | Expanded in vivo substrate profile of the yeast N-terminal acetyltransferase NatC. |
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| المؤلفون: | Van Damme P; iRIP Unit, Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium. Electronic address: petra.vandamme@ugent.be., Osberg C; Department of Biomedicine, University of Bergen, Bergen, Norway., Jonckheere V; iRIP Unit, Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium., Glomnes N; Department of Biomedicine, University of Bergen, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway., Gevaert K; VIB-UGent Center for Medical Biotechnology, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium., Arnesen T; Department of Biomedicine, University of Bergen, Bergen, Norway; Department of Biological Sciences, University of Bergen, Bergen, Norway; Department of Surgery, Haukeland University Hospital, Bergen, Norway., Aksnes H; Department of Biomedicine, University of Bergen, Bergen, Norway. Electronic address: henriette.aksnes@uib.no. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2023 Feb; Vol. 299 (2), pp. 102824. Date of Electronic Publication: 2022 Dec 22. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | N-Terminal Acetyltransferases*/deficiency , N-Terminal Acetyltransferases*/genetics , N-Terminal Acetyltransferases*/metabolism , Saccharomyces cerevisiae*/enzymology , Saccharomyces cerevisiae*/metabolism, Humans ; Acetylation ; Chromatography, Liquid ; Conserved Sequence ; Genetic Complementation Test ; Methionine/metabolism ; N-Terminal Acetyltransferase C/genetics ; N-Terminal Acetyltransferase C/metabolism ; N-Terminal Acetyltransferase E ; Phenotype ; Protein Processing, Post-Translational ; Substrate Specificity |
| مستخلص: | N-terminal acetylation is a conserved protein modification among eukaryotes. The yeast Saccharomyces cerevisiae is a valuable model system for studying this modification. The bulk of protein N-terminal acetylation in S. cerevisiae is catalyzed by 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 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 naa30Δ 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 the lack of NatC-mediated N-terminal acetylation to phenotypes of NatC deletion yeast. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: N-alpha-acetyltransferase 30; N-terminal acetylation; N-terminal acetylome; S. cerevisiae disease model; glycerol metabolism; mitochondrial metabolism; non-fermentable sugar phenotype; protein modification; subcellular fractionation; virus assembly |
| المشرفين على المادة: | AE28F7PNPL (Methionine) EC 2.3.1.256 (N-Terminal Acetyltransferase C) EC 2.3.1.258 (N-Terminal Acetyltransferase E) EC 2.3.1.88 (N-Terminal Acetyltransferases) EC 2.3.1.256 (NAA30 protein, human) EC 2.3.1.- (NatA protein, S cerevisiae) EC 2.3.1.- (NatB protein, S cerevisiae) EC 2.3.1.256 (MAK3 protein, S cerevisiae) |
| تواريخ الأحداث: | Date Created: 20221225 Date Completed: 20240123 Latest Revision: 20240123 |
| رمز التحديث: | 20240124 |
| مُعرف محوري في PubMed: | PMC9867985 |
| DOI: | 10.1016/j.jbc.2022.102824 |
| PMID: | 36567016 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2022.102824 |