title: Folded HasA inhibits its own secretion through its ABC exporter.
abstract: Gram-negative bacterial proteins secreted by ABC exporters carry a secretion signal in their carboxylic extremities. This characteristic suggests that the polypeptide needs to be fully synthesized before it can be secreted and, therefore, presumably may fold at least in part before its secretion. We investigated the relationship between folding and secretion using HasA, a hemoprotein of Serratia marcescens secreted into the extracellular medium by a dedicated Has ABC exporter. We first demonstrated that when HasA is sequestered in the cytoplasm it can acquire its tertiary structure, as assessed from its capacity to bind heme. The cytoplasmic pool of HasA cannot be secreted and inhibits the secretion of newly synthesized molecules. HasA folding in the cytoplasm was independent of either its capacity to bind heme or the presence of SecB, although SecB is essential for HasA secretion. Our findings indicate a strong coupling between synthesis and secretion in the type I secretion pathway.
authors.affiliation: Unité des Membranes Bactériennes, Institut Pasteur, 25 Rue du Dr Roux, 75024 Paris Cedex 15, France.
authors.forename: L
authors.initials: L
authors.lastname: Debarbieux
authors.forename: C
authors.initials: C
authors.lastname: Wandersman
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D005838:Genotype; D006418:Heme / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D010957:Plasmids; D017510:Protein Folding; D011994:Recombinant Proteins / Q000378:metabolism; D012706:Serratia marcescens / Q000235:genetics / Q000502:physiology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D002352:Carrier Proteins; C093956:HasA protein, Serratia marcescens; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins; C057842:SecB protein, Bacteria; D006418:Heme