title: The crystal structure of filamentous hemagglutinin secretion domain and its implications for the two-partner secretion pathway.
abstract: Filamentous hemagglutinin (FHA), the major 230-kDa adhesin of the whooping cough agent Bordetella pertussis, is one of the most efficiently secreted proteins in Gram-negative bacteria. FHA is secreted by means of the two-partner secretion (TPS) pathway. Several important human, animal, and plant pathogens also secrete adhesins and other virulence factors by using this mode of secretion. A TPS system is composed of two separate proteins, with TpsA the secreted protein and TpsB its associated specific outermembrane transporter. All TPS-secreted proteins contain a distinctive N-proximal module essential for secretion, the TPS domain. We report here the 1.7- A structure of a functionally secreted 30-kDa N-terminal fragment of FHA. It reveals that the TPS domain folds into a beta-helix, with three extrahelical motifs, a beta-hairpin, a four-stranded beta-sheet, and an N-terminal capping, mostly formed by the nonconserved regions of the TPS domain. The structure thus explains why the TPS domain is able to initiate folding of the beta-helical motifs that form the central domain of the adhesin, because it is itself a beta-helical scaffold. It also contains less conserved extrahelical regions most likely involved in specific properties, such as the recognition of the outer-membrane transporter. This structure is representative of the TPS domains found so far in >100 secreted proteins from pathogenic bacteria. It also provides a mechanistic insight into how protein folding may be linked to secretion in the TPS pathway.
authors.affiliation: Institut Fédératif de Recherche du Centre National de la Recherche Scientifique 3, Lille Cedex, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Clantin
authors.forename: Hélène
authors.initials: H
authors.lastname: Hodak
authors.forename: Eve
authors.initials: E
authors.lastname: Willery
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.forename: Françoise
authors.initials: F
authors.lastname: Jacob-Dubuisson
authors.forename: Vincent
authors.initials: V
authors.lastname: Villeret
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D006388:Hemagglutinins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D010566:Virulence Factors, Bordetella / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D017931:DNA Primers; D006388:Hemagglutinins; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis