Structural and functional characterization of two-partner secretion systems of pathogenic Gram-negative bacteria


Gram-negative bacteria have evolved various pathways to secrete proteins into the extracellular medium. One of them is the two-partner secretion system (TPS), which is present in many Gram-negative bacteria and is often involved in pathogenesis. For example, in Bordetella pertussis, the causative agent of whooping cough, TPS is responsible for the secretion of filamentous haemagglutinin, which mediates the adhesion of the bacteria to cilia cells of the tracheal tract. In the TPS pathway, the exoprotein is transported over the outer membrane by a single outer-membrane-integrated transporter protein. The transport mechanism is largely unknown. The aim of this study is to solve the crystal structure of the transporter protein alone and in complex with the exoprotein. Such structural information will provide much insight into the mechanism of transport by the TPS system The TPS transporter proteins share homology with the conserved protein Omp85, a protein that is essential for the correct membrane insertion of outer membrane proteins. Furthermore, homologues of the transporter proteins have been found in eukaryotes, where they play an essential role in the biogenesis of mitochondria and chloroplasts. Solving the structure of a B. pertussis TPS-transporter protein and exoprotein will provide fundamental insight into the protein-translocation process of the TPS and of its prokaryotic and eukaryotic homologues. In addition, such structural information may be beneficial to the development of a new B. pertussis vaccine, which is urgently needed, and to the design of new antimicrobials.


Wetenschappelijk artikel

  • P. van der Ley, W. Lambert, J.J. Smolenaers, A.M. Bonvin, L. Rutten, M.R. Egmond, J. Geurtsen, J. Tommassen, P. Gros, A. de Haan(2006): Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from Pseudomonas aeruginosa. Proc Natl Acad Sci U S A pp. 7071 - 7076
  • M.P. Bos, S.A. Muller, J. Tommassen, M. Gregorini, J. Kortekaas, P. Ringler, V.E. Weynants, L. Rutten(2006): Immunogenicity and structural characterisation of an in vitro folded meningococcal siderophore receptor (FrpB, FetA). Microbes Infect. pp. 2145 - 2153





Dr. L. Rutten

Verbonden aan

Universiteit Utrecht, Faculteit Bètawetenschappen, Departement Biologie


Dr. L. Rutten


01/12/2004 tot 04/03/2008