title: Conditional Proteolysis of the Membrane Protein YfgM by the FtsH Protease Depends on a Novel N-terminal Degron.
abstract: 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 to that 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. On the basis of these and other results in the literature, we propose a model for how the membrane-spanning YfgM protein serves as connector between the stress responses in the periplasm and cytoplasm.
authors.affiliation: From Microbial Biology, Ruhr University Bochum, 44801 Bochum, Germany.
authors.forename: Lisa-Marie
authors.initials: LM
authors.lastname: Bittner
authors.affiliation: From Microbial Biology, Ruhr University Bochum, 44801 Bochum, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Westphal
authors.affiliation: From Microbial Biology, Ruhr University Bochum, 44801 Bochum, Germany franz.narberhaus@rub.de.
authors.forename: Franz
authors.initials: F
authors.lastname: Narberhaus
mesh_terms: D049069:ATP-Dependent Proteases / Q000502:physiology*; D000595:Amino Acid Sequence; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D055550:Protein Stability; D059748:Proteolysis; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; C489568:RcsB protein, E coli; D014157:Transcription Factors; C000592363:YfgM protein, E coli; D049069:ATP-Dependent Proteases; C513383:FtsH protein, E coli; C530413:PpiD protein, E coli; D019696:Peptidylprolyl Isomerase
keywords: ATP-dependent protease; Escherichia coli (E. coli); Rcs phosphorelay system; protease; protein degradation; stress response