Rhomboid intramembrane protease YqgP licenses bacterial membrane protein quality control as adaptor of FtsH AAA protease

• Jakub Began ^[1] ; Baptiste Cordier ^[2] ; Jana Březinová ^[1] ; Jordan Delisle ^[2] ; Rozálie Hexnerová ^[3] ; Pavel Srb ^[3] ; Petra Rampírová ^[3] ; Milan Kožíšek ^[3] ; Mathieu Baudet ^[4] ; Yohann Couté ^[4] ; Anne Galinier ^[2] ; Václav Veverka ^[1] ; Thierry Doan ^[5] ; Kvido Strisovsky ^[3]
  1. [1] Institute of Organic Chemistry

     Institute of Organic Chemistry

     Ucrania

     
  2. [2] Institut de Microbiologie de la Méditerranée

     Institut de Microbiologie de la Méditerranée

     Arrondissement de Marseille, Francia

     
  3. [3] Institute of Organic Chemistry and Biochemistry

     Institute of Organic Chemistry and Biochemistry

     Chequia

     
  4. [4] Grenoble Alpes University

     Grenoble Alpes University

     Arrondissement de Grenoble, Francia

     
  5. [5] 3 Laboratoire de Chimie Bactérienne (LCB) Institut de Microbiologie de la Méditerranée (IMM) CNRS, UMR 7283 Aix Marseille Univ Marseille Cedex 20 France; 7 Laboratoire d'Ingénierie des Systèmes Macromoléculaires (LISM) Institut de Microbiologie de la Méditerranée (IMM) CNRS, UMR 7255 Aix Marseille Univ Marseille Cedex 20 France

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 39, Nº. 10, 2020
• Idioma: inglés
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  • Magnesium homeostasis is essential for life and depends on magnesium transporters, whose activity and ion selectivity need to be tightly controlled. Rhomboid intramembrane proteases pervade the prokaryotic kingdom, but their functions are largely elusive. Using proteomics, we find that Bacillus subtilis rhomboid protease YqgP interacts with the membrane‐bound ATP‐dependent processive metalloprotease FtsH and cleaves MgtE, the major high‐affinity magnesium transporter in B. subtilis. MgtE cleavage by YqgP is potentiated in conditions of low magnesium and high manganese or zinc, thereby protecting B. subtilis from Mn2+/Zn2+ toxicity. The N‐terminal cytosolic domain of YqgP binds Mn2+ and Zn2+ ions and facilitates MgtE cleavage. Independently of its intrinsic protease activity, YqgP acts as a substrate adaptor for FtsH, a function that is necessary for degradation of MgtE. YqgP thus unites protease and pseudoprotease function, hinting at the evolutionary origin of rhomboid pseudoproteases such as Derlins that are intimately involved in eukaryotic ER‐associated degradation (ERAD). Conceptually, the YqgP‐FtsH system we describe here is analogous to a primordial form of “ERAD” in bacteria and exemplifies an ancestral function of rhomboid‐superfamily proteins.