Download MendeleyThe crystal structure of filamentous hemagglutinin secretion domain and its implications for the two-partner secretion pathway
Clantin, B., Hodak, H., Willery, E., Locht, C., Jacob-Dubuisson, F., Villeret, V.(2004) Proc Natl Acad Sci U S A 101: 6194-6199
- PubMed: 15079085
- DOI: https://doi.org/10.1073/pnas.0400291101
- Primary Citation of Related Structures:
1RWR - PubMed 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.
Organizational Affiliation:
Institut Fédératif de Recherche du Centre National de la Recherche Scientifique 3, Lille Cedex, France.
