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Article

  • The EMBO Journal (2006) 25, 2297 - 2304
  • doi:10.1038/sj.emboj.7601132

Published online: 11 May 2006

Structure of the outer membrane translocator domain of the Haemophilus influenzae Hia trimeric autotransporter

Guoyu Meng1,a, Neeraj K Surana2,3,a, Joseph W St Geme III2,3,4,5 and Gabriel Waksman1

  1. Institute of Structural Molecular Biology at UCL/Birkbeck, London, UK
  2. The Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA
  3. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA
  4. Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
  5. Department Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA

Correspondence to:

Gabriel Waksman, Birkbeck College, School of Crystallography, Malet Street, London WC1E 7HX, UK. Tel.: +44 0207 631 6833; Fax: +44 0207 631 6833; E-mail: g.waksman@mail.cryst.bbk.ac.uk

Joseph W St Geme III, Department of Pediatrics, Duke University Medical Center, T901 Children's Health Center, Durham, NC 27710, USA. Tel.: +1 919 681 4080; Fax: +1 919 681 2714; E-mail: j.stgeme@duke.edu

aThese authors contributed equally to this work

Received 14 March 2006; Accepted 12 April 2006

Autotransporter proteins are defined by the ability to drive their own secretion across the bacterial outer membrane. The Hia autotransporter of Haemophilus influenzae belongs to the trimeric autotransporter subfamily and mediates bacterial adhesion to the respiratory epithelium. In this report, we present the crystal structure of the C-terminal end of Hia, corresponding to the entire Hia translocator domain and part of the passenger domain (residues 992–1098). This domain forms a beta-barrel with 12 transmembrane beta-strands, including four strands from each subunit. The beta-barrel has a central channel of 1.8 nm in diameter that is traversed by three N-terminal alpha-helices, one from each subunit. Mutagenesis studies demonstrate that the transmembrane portion of the three alpha-helices and the loop region between the alpha-helices and the neighboring beta-strands are essential for stability of the trimeric structure of the translocator domain, and that trimerization of the translocator domain is a prerequisite for translocator activity. Overall, this study provides important insights into the mechanism of translocation in trimeric autotransporters.

  • Keywords:

    • adhesion,
    • crystal structure,
    • microbial pathogenesis,
    • protein secretion,
    • trimeric autotransporter