Conditional Proteolysis of the Membrane Protein YfgM by FtsH Depends on a Novel N-terminal Degron [Protein Synthesis and Degradation]

June 19th, 2015 by Bittner, L.-M., Westphal, K., Narberhaus, F.

Regulated proteolysis efficiently and rapidly adapts the bacterial proteome to changing environmental conditions. Many protease substrates contain recognition motifs so-called degrons that direct them to the appropriate protease. Here, we describe an entirely new degron identified in the cytoplasmic N-terminal end of the membrane-anchored protein YfgM of Escherichia coli. YfgM is stable during exponential growth and degraded in stationary phase by the essential FtsH protease. The alarmone (p)ppGpp but not the previously described YfgM interactors RcsB and PpiD influence YfgM degradation. By scanning mutagenesis, we define individual amino acids responsible for turnover of YfgM and find that the degron does not at all comply with the known N-end rule pathway. The YfgM degron is a distinct module that facilitates FtsH-mediated degradation when fused to the N terminus of another monotopic membrane protein but not of a cytoplasmic protein. Several lines of evidence suggest that stress-induced degradation of YfgM relieves the response regulator RcsB and thereby permits cellular protection by the Rcs phosphorelay system. Based on these and other results in the literature, we propose a model how the membrane-spanning YfgM protein serves as connector between the stress responses in the periplasm and cytoplasm.