The research in Strisovsky lab is focused on biological membranes and enzymatic catalysis occurring in their context. We are studying the ubiquitous intramembrane proteases of the rhomboid family and the mechanistic aspects of their functions relevant for biological signaling, membrane protein biogenesis and homeostasis. In our work we integrate the tools of membrane biochemistry, enzymology and structural biology to understand how rhomboid proteases recognise and select substrates, and employ methods of quantitative proteomics, cell biology and genetics to uncover molecular basis of rhomboid functions in organisms. We are an international group and we are always eager to consider motivated students and postdocs who would like to join us. If interested, contact Kvido Strisovsky.
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.