title: Structure of a Type-1 Secretion System ABC Transporter.
abstract: Type-1 secretion systems (T1SSs) represent a widespread mode of protein secretion across the cell envelope in Gram-negative bacteria. The T1SS is composed of an inner-membrane ABC transporter, a periplasmic membrane-fusion protein, and an outer-membrane porin. These three components assemble into a complex spanning both membranes and providing a conduit for the translocation of unfolded polypeptides. We show that ATP hydrolysis and assembly of the entire T1SS complex is necessary for protein secretion. Furthermore, we present a 3.15-Å crystal structure of AaPrtD, the ABC transporter found in the Aquifex aeolicus T1SS. The structure suggests a substrate entry window just above the transporter's nucleotide binding domains. In addition, highly kinked transmembrane helices, which frame a narrow channel not observed in canonical peptide transporters, are likely involved in substrate translocation. Overall, the AaPrtD structure supports a polypeptide transport mechanism distinct from alternating access.
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, 480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA. Electronic address: jlm2qp@virginia.edu.
authors.forename: Jacob L W
authors.initials: JLW
authors.lastname: Morgan
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, 480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA.
authors.forename: Justin F
authors.initials: JF
authors.lastname: Acheson
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, 480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA. Electronic address: jochen_zimmer@virginia.edu.
authors.forename: Jochen
authors.initials: J
authors.lastname: Zimmer
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry; D018360:Crystallography, X-Ray; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D000069177:Type I Secretion Systems / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D000069177:Type I Secretion Systems; D000255:Adenosine Triphosphate
keywords: ABC transporter; bacterial virulence; protein translocation; type 1 secretion system