The Crystal Structure of Filamentous Hemagglutinin Secretion Domain and Its Implications for the Two-Partner Secretion Pathway
Filamentous hemagglutinin (FHA), the major 230-kDa adhesin of the whooping cought 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 pa...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 16; pp. 6194 - 6199 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
20.04.2004
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Filamentous hemagglutinin (FHA), the major 230-kDa adhesin of the whooping cought 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 outer-membrane transporter. All TPS-secreted proteins contain a distinctive N-proximal module essential for secretion, the TPS domain. We report here the 1.7-Å structure of a functionally secreted 30-kDa N-terminal fragment of FHA. It reveals that the TPS domain folds into a β-helix, with three extrahelical motifs, a β-hairpin, a four-stranded β-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 β-helical motifs that form the central domain of the adhesin, because it is itself a β-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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 F.J.-D. and V.V. contributed equally to the work. This paper was submitted directly (Track II) to the PNAS office. Abbreviations: FHA, filamentous hemagglutinin; TPS, two-partner secretion; AT, autotransporter. Edited by William N. Lipscomb, Harvard University, Cambridge, MA Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 1RWR). To whom correspondence may be addressed. E-mail: francoise.jacob@pasteur-lille.fr or vincent.villeret@ibl.fr. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0400291101 |