Investigating Peptide-Coenzyme A Conjugates as Chemical Probes for Proteomic Profiling of N-Terminal and Lysine Acetyltransferases

Autor:	Julia Sindlinger, Stefan Schön, Jürgen Eirich, Sören Kirchgäßner, Iris Finkemeier, Dirk Schwarzer
Rok vydání:	2022
Předmět:	Proteomics Acetyltransferases Lysine Organic Chemistry Molecular Medicine Acetylation Coenzyme A Lysine Acetyltransferases Peptides Molecular Biology Biochemistry
Zdroj:	Chembiochem : a European journal of chemical biology. 23(17)
ISSN:	1439-7633
Popis:	Acetyl groups are transferred from acetyl-coenzyme A (Ac-CoA) to protein N-termini and lysine side chains by N-terminal acetyltransferases (NATs) and lysine acetyltransferases (KATs), respectively. Building on lysine-CoA conjugates as KAT probes, we have synthesized peptide probes with CoA conjugated to N-terminal alanine (α-Ala-CoA), proline (α-Pro-CoA) or tri-glutamic acid (α-3Glu-CoA) units for interactome profiling of NAT complexes. The α-Ala-CoA probe enriched the majority of NAT catalytic and auxiliary subunits, while a lysine CoA-conjugate bound only a subset of endogenous KATs. Interactome profiling with the α-Pro-CoA probe showed reduced NAT recruitment in favor of metabolic CoA binding proteins and α-3Glu-CoA steered the interactome towards NAA80 and NatB. These findings agreed with the inherent substrate specificities of the target proteins and showed that N-terminal CoA-conjugated peptides are versatile probes for NAT complex profiling in lysates of physiological and pathological backgrounds.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd872dd5ac8756af77b789a3e92084c4 https://pubmed.ncbi.nlm.nih.gov/35776679 Zobrazit plný text záznamu Plný text