title: Structural analysis of DegS, a stress sensor of the bacterial periplasm.
abstract: Regulated proteolysis is a key event in transmembrane signalling between intracellular compartments. In Escherichia coli the membrane-bound protease DegS has been identified as the periplasmic stress sensor for unfolded outer membrane proteins (OMPs). DegS inititates a proteolytic cascade resulting in the release of sigmaE the transcription factor of periplasmic genes. The crystal structure of DegS protease reported at 2.2 A resolution reveals a trimeric complex with the monomeric protease domain in an inhibited state followed by the inhibitory PDZ domain. Noteably, domain architecture and communication of DegS are remarkably to homologous proteins known to date. Here the domain interface is mechanically locked by three intradomain salt bridges. Co-crystallisation trials in the presence of a 10-residue activating peptide did not result in significant structural intradomain shifts nor distortions in the crystal packing. These observations imply a mode of activation indicative of peptide-induced structural shifts imposed to the protease domain rather than disturbing the PDZ-protease interface.
authors.affiliation: Department of Membrane Biochemistry, Max-Planck-Institute for Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany. zeth@biochem.mpg.de
authors.forename: Kornelius
authors.initials: K
authors.lastname: Zeth
mesh_terms: D000595:Amino Acid Sequence; D001419:Bacteria / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C066496:DegS protein, Bacteria; D029968:Escherichia coli Proteins; C489349:degS protein, Escherichia coli