title: Channel properties of TpsB transporter FhaC point to two functional domains with a C-terminal protein-conducting pore.
abstract: Integral outer membrane transporters of the Omp85/TpsB superfamily mediate the translocation of proteins across, or their integration into, the outer membranes of Gram-negative bacteria, chloroplasts, and mitochondria. The Bordetella pertussis FhaC/FHA couple serves as a model for the two-partner secretion pathway in Gram-negative bacteria, with the TpsB protein, FhaC, being the specific transporter of its TpsA partner, FHA, across the outer membrane. In this work, we have investigated the structure/function relationship of FhaC by analyzing the ion channel properties of the wild type protein and a collection of mutants with varied FHA secretion activities. We demonstrated that the channel is formed by the C-terminal two-thirds of FhaC most likely folding into a beta-barrel domain predicted to be conserved throughout the family. A C-proximal motif that represents the family signature appears essential for pore function. The N-terminal 200 residues of FhaC constitute a functionally distinct domain that modulates the pore properties and may participate in FHA recognition.
authors.affiliation: UMR 5048 CNRS, U554 INSERM, Centre de Biochimie Structurale, 29 Rue de Navacelles, 34090 Montpellier Cedex, France.
authors.forename: Albano C
authors.initials: AC
authors.lastname: Méli
authors.forename: Hélène
authors.initials: H
authors.lastname: Hodak
authors.forename: Bernard
authors.initials: B
authors.lastname: Clantin
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.forename: Gérard
authors.initials: G
authors.lastname: Molle
authors.forename: Françoise
authors.initials: F
authors.lastname: Jacob-Dubuisson
authors.forename: Nathalie
authors.initials: N
authors.lastname: Saint
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D001886:Bordetella pertussis / Q000235:genetics / Q000378:metabolism*; D007477:Ions / Q000378:metabolism; D008051:Lipid Bilayers; D008564:Membrane Potentials / Q000502:physiology; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D007477:Ions; D008051:Lipid Bilayers; C098052:fhaC protein, Bordetella pertussis