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  • The EMBO Journal (2002) 21, 3286 - 3295
  • doi:10.1093/emboj/cdf329

Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE

Gretel Buchwald1, Andrea Friebel2, Jorge E. Galán3, Wolf-Dietrich Hardt4, Alfred Wittinghofer1 and Klaus Scheffzek5

  1. Max-Planck-Institut für Molekulare Physiologie, Abt. Strukturelle Biologie, Otto-Hahn-Str. 11, D-44227 Dortmund, Germany
  2. Max von Pettenkofer-Insitut, Pettenkoferstr. 9a, D-80336 München, Germany
  3. Section of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536, USA
  4. Institute of Microbiology, ETHZ/LFV B20, Schmelzberg Str. 7, 8092 Zürich, Switzerland
  5. European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Programme, Meyerhofstr. 1, D-69117 Heidelberg, Germany

Correspondence to:

Klaus Scheffzek, E-mail: Klaus.Scheffzek@embl-heidelberg.de

Alfred Wittinghofer, E-mail: Alfred.Wittinghofer@mpi-dortmund.mpg.de

Received 25 January 2002; Accepted 6 May 2002; Revised 26 April 2002

The bacterial enteropathogen Salmonella typhimurium employs a type III secretion system to inject bacterial toxins into the host cell cytosol. These toxins transiently activate Rho family GTP-binding protein-dependent signaling cascades to induce cytoskeletal rearrangements. One of these translocated Salmonella toxins, SopE, can activate Cdc42 in a Dbl-like fashion despite its lack of sequence similarity to Dbl-like proteins, the Rho-specific eukaryotic guanine nucleotide exchange factors. To elucidate the mechanism of SopE-mediated guanine nucleotide exchange, we have analyzed the structure of the complex between a catalytic fragment of SopE and Cdc42. SopE binds to and locks the switch I and switch II regions of Cdc42 in a conformation that promotes guanine nucleotide release. This conformation is strikingly similar to that of Rac1 in complex with the eukaryotic Dbl-like exchange factor Tiam1. However, the catalytic domain of SopE has an entirely different architecture from that of Tiam1 and interacts with the switch regions via different amino acids. Therefore, SopE represents the first example of a non-Dbl-like protein capable of inducing guanine nucleotide exchange in Rho family proteins.

  • Keywords:

    • cytoskeleton,
    • Dbl,
    • GEF,
    • GTP binding,
    • Salmonella