title: Overflow of a hyper-produced secretory protein from the Bacillus Sec pathway into the Tat pathway for protein secretion as revealed by proteogenomics.
abstract: Bacteria secrete numerous proteins into their environment for growth and survival under complex and ever-changing conditions. The highly different characteristics of secreted proteins pose major challenges to the cellular protein export machinery and, accordingly, different pathways have evolved. While the main secretion (Sec) pathway transports proteins in an unfolded state, the twin-arginine translocation (Tat) pathway transports folded proteins. To date, these pathways were believed to act in strictly independent ways. Here, we have employed proteogenomics to investigate the secretion mechanism of the esterase LipA of Bacillus subtilis, using a serendipitously obtained hyper-producing strain. While LipA is secreted Sec-dependently under standard conditions, hyper-produced LipA is secreted predominantly Tat-dependently via an unprecedented overflow mechanism. Two previously identified B. subtilis Tat substrates, PhoD and YwbN, require each a distinct Tat translocase for secretion. In contrast, hyper-produced LipA is transported by both Tat translocases of B. subtilis, showing that they have distinct but overlapping specificities. The identified overflow secretion mechanism for LipA focuses interest on the possibility that secretion pathway choice can be determined by environmental and intracellular conditions. This may provide an explanation for the previous observation that many Sec-dependently transported proteins have potential twin-arginine signal peptides for export via the Tat pathway.
authors.affiliation: Department of Medical Microbiology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
authors.forename: Thijs R H M
authors.initials: TR
authors.lastname: Kouwen
authors.forename: René
authors.initials: R
authors.lastname: van der Ploeg
authors.forename: Haike
authors.initials: H
authors.lastname: Antelmann
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mäder
authors.forename: Jan Maarten
authors.initials: JM
authors.lastname: van Dijl
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D015180:Electrophoresis, Gel, Two-Dimensional; D023281:Genomics / Q000379:methods; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D040901:Proteomics / Q000379:methods; D055571:Secretory Pathway / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C079999:LipA protein, Bacteria; D026901:Membrane Transport Proteins