Phosphorylation of the acyl-CoA binding pocket of the FadR transcription regulator in Sulfolobus acidocaldarius

Hassan R Maklad, Gustavo J Gutierrez, Dominik Esser, Bettina Siebers, Eveline Peeters

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The archaeal model organism Sulfolobus acidocaldarius possesses a TetR-like transcription factor that represses a 30-kb gene cluster encoding fatty acid metabolism enzymes. Interaction of this regulator, FadR, with acyl-CoA molecules causes a DNA dissociation, which may lead to a derepression of the gene cluster. Previously, a phosphoproteome analysis revealed the phosphorylation of three consecutive amino acids in the acyl-CoA ligand binding pocket. Here, we study this phosphorylation event and show that ArnC, a Hanks-type protein kinase, targets a threonine within the phosphoacceptor motif in vitro. Electrophoretic mobility shift assays using a phosphomimetic mutant of FadR demonstrate that the presence of negatively charged groups on the phosphoacceptor motif causes an inhibition of the ligand binding that desensitizes the responsiveness of the regulator to acyl-CoA molecules. Based on these observations, we propose a model in which phosphorylation of FadR in its ligand-binding pocket acts as an additional regulatory layer silencing acyl-CoA responsive derepression of fatty acid and lipid degradation. Moreover, given the recently discovered interplay between FadR and the chromosome structuring protein Coalescin, FadR phosphorylation could also influence local chromosome conformation under specific cellular conditions.

Original languageEnglish
Pages (from-to)120-124
Number of pages5
JournalBiochimie
Volume175
DOIs
Publication statusPublished - 26 Jun 2020

Bibliographical note

Copyright © 2020. Published by Elsevier B.V.

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