Structural mimicry for vinculin activation by IpaA, a virulence factor of Shigella flexneri

Cyril Hamiaux, André van Eerde, Claude Parsot, Jaap Broos, Bauke W Dijkstra

Author Affiliations

  1. Cyril Hamiaux1,,
  2. André van Eerde1,,
  3. Claude Parsot2,
  4. Jaap Broos1 and
  5. Bauke W Dijkstra*,1
  1. 1 Laboratory of Biophysical Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands
  2. 2 Unité de Pathogénie Microbienne Moléculaire INSERM U786, Institut Pasteur, 28 rue du Docteur Roux, 75724, Paris, Cedex 15, France
  1. *Corresponding author. Tel: +31 50 363 4381/4378; Fax: +31 50 363 4800; E‐mail: b.w.dijkstra{at}
  1. These authors contributed equally to this work

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Invasion of epithelial cells by Shigella flexneri is characterized by cytoskeletal rearrangements of the host cell membrane, promoting internalization of the bacterium. The bacterial effector IpaA is injected into the epithelial cell by a type III secretion apparatus and recruits vinculin to regulate actin polymerization at the site of entry. We analysed the complex formed between a carboxy‐terminal fragment of IpaA (IpaA560−633) and the vinculin D1 domain (VD1), both in crystals and in solution. We present evidence that IpaA560−633 has two α‐helical vinculin‐binding sites that simultaneously bind two VD1 molecules. The interaction of IpaA560−633 with VD1 is highly similar to the interaction of the endogenous, eukaryotic proteins talin and α‐actinin with VD1, showing that Shigella uses a structural mimicry strategy to activate vinculin.

  • Received April 24, 2006.
  • Revision received June 14, 2006.
  • Accepted June 14, 2006.
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