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Article

  • The EMBO Journal (2004) 23, 1257 - 1266
  • doi:10.1038/sj.emboj.7600148

Published online: 11 March 2004

Structure of the translocator domain of a bacterial autotransporter

Clasien J Oomen1,2,a, Peter van Ulsen2,3,a, Patrick Van Gelder4, Maya Feijen3, Jan Tommassen3 and Piet Gros1

  1. Department of Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands
  2. Netherlands Vaccine Institute, Bilthoven, The Netherlands
  3. Department of Molecular Microbiology, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
  4. Department of Molecular and Cellular Interactions, Flemish Interuniversity Institute for Biotechnology, Free University Brussels, Brussels, Belgium

Correspondence to:

Piet Gros, Department of Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, Utrecht CH 3584, The Netherlands. Tel.: +31 30 253 3127; Fax: +31 30 253 3940; E-mail: p.gros@chem.uu.nl

aThese authors contributed equally to this work

Received 27 June 2003; Accepted 6 February 2004

Autotransporters are virulence-related proteins of Gram-negative bacteria that are secreted via an outer-membrane-based C-terminal extension, the translocator domain. This domain supposedly is sufficient for the transport of the N-terminal passenger domain across the outer membrane. We present here the crystal structure of the in vitro-folded translocator domain of the autotransporter NalP from Neisseria meningitidis, which reveals a 12-stranded beta-barrel with a hydrophilic pore of 10 times 12.5 Å that is filled by an N-terminal alpha-helix. The domain has pore activity in vivo and in vitro. Our data are consistent with the model of passenger-domain transport through the hydrophilic channel within the beta-barrel, and inconsistent with a model for transport through a central channel formed by an oligomer of translocator domains. However, the dimensions of the pore imply translocation of the secreted domain in an unfolded form. An alternative model, possibly covering the transport of folded domains, is that passenger-domain transport involves the Omp85 complex, the machinery required for membrane insertion of outer-membrane proteins, on which autotransporters are dependent.

  • Keywords:

    • autotransporters,
    • crystal structure,
    • Neisseria meningitidis,
    • outer-membrane protein,
    • protein secretion