title: Preprotein mature domains contain translocase targeting signals that are essential for secretion.
abstract: Secretory proteins are only temporary cytoplasmic residents. They are typically synthesized aspreproteins, carrying signal peptides N-terminally fused to their mature domains. In bacteria secretion largely occurs posttranslationally through the membrane-embedded SecA-SecYEG translocase. Upon crossing the plasma membrane, signal peptides are cleaved off and mature domains reach their destinations and fold. Targeting to the translocase is mediated by signal peptides. The role of mature domains in targeting and secretion is unclear. We now reveal that mature domains harbor their own independent targeting signals (mature domain targeting signals [MTSs]). These are multiple, degenerate, interchangeable, linear or 3D hydrophobic stretches that become available because of the unstructured states of targeting-competent preproteins. Their receptor site on the cytoplasmic face of the SecYEG-bound SecA is also of hydrophobic nature and is located adjacent to the signal peptide cleft. Both the preprotein MTSs and their receptor site on SecA are essential for protein secretion. Evidently, mature domains have their own previously unsuspected distinct roles in preprotein targeting and secretion.
authors.affiliation: Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Katerina E
authors.identifier: 0000-0002-8100-4382
authors.initials: KE
authors.lastname: Chatzi
authors.affiliation: Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Marios Frantzeskos
authors.identifier: 0000-0001-7337-3105
authors.initials: MF
authors.lastname: Sardis
authors.affiliation: Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Tsirigotaki
authors.affiliation: Institute of Molecular Biology and Biotechnology FoRTH, Iraklio, 71110 Crete, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Koukaki
authors.affiliation: Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Šoštarić
authors.affiliation: Biomolecular and Analytical Mass Spectrometry Group, Department of Chemistry, University of Antwerp, 2000 Antwerp, Belgium.
authors.forename: Albert
authors.initials: A
authors.lastname: Konijnenberg
authors.affiliation: Biomolecular and Analytical Mass Spectrometry Group, Department of Chemistry, University of Antwerp, 2000 Antwerp, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Charalampos G
authors.initials: CG
authors.lastname: Kalodimos
authors.affiliation: Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Spyridoula
authors.initials: S
authors.lastname: Karamanou
authors.affiliation: Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium tassos.economou@kuleuven.be.|Institute of Molecular Biology and Biotechnology FoRTH, Iraklio, 71110 Crete, Greece.
authors.forename: Anastassios
authors.identifier: 0000-0002-1770-507X
authors.initials: A
authors.lastname: Economou
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000166:cytology / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D000072417:Protein Domains; D021382:Protein Sorting Signals; D000069816:SEC Translocation Channels / Q000378:metabolism*; D000081416:SecA Proteins
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D021382:Protein Sorting Signals; D000069816:SEC Translocation Channels; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins