Fiche publication
Date publication
novembre 2023
Journal
The FEBS journal
Auteurs
Membres identifiés du Cancéropôle Est :
Dr TRAVE Gilles
,
Dr NEGRONI Luc
,
Mr EBERLING Pascal
,
Mr MORLET Bastien
,
Dr GOGL Gergo
Tous les auteurs :
Zambo B, Gogl G, Morlet B, Eberling P, Negroni L, Moine H, Travé G
Lien Pubmed
Résumé
Diacylglycerol kinases (DGKs) control local and temporal amounts of diacylglycerol (DAG) and phosphatidic acid (PA) by converting DAG to PA through phosphorylation in cells. Certain DGK enzymes possess C-terminal sequences that encode potential PDZ-binding motifs (PBMs), which could be involved in their recruitment into supramolecular signaling complexes. In this study, we used two different interactomic approaches, quantitative native holdup (nHU) and qualitative affinity purification (AP), both coupled to mass spectrometry (MS) to investigate the PDZ partners associated with the potential PBMs of DGKs. Complementing these results with site-specific affinity interactomic data measured on isolated PDZ domain fragments and PBM motifs, as well as evolutionary conservation analysis of the PBMs of DGKs, we explored functional differences within different DGK groups. All our results indicate that putative PBM sequences of type II enzymes, namely DGKδ, DGKη and DGKκ, are likely to be nonfunctional. In contrast, type IV enzymes, namely DGKζ and DGKι, possess highly promiscuous PBMs that interact with a set of PDZ proteins with very similar affinity interactomes. The combination of various interactomic assays and evolutionary analyses provides a useful strategy for identifying functional domains and motifs within diverse enzyme families.
Mots clés
DGK, PDZ domain, PDZ-binding motif, diacylglycerol kinase, interactome
Référence
FEBS J. 2023 11 9;:
