||Cesar Valencia-Gallardo, Daniel-Isui Aguilar-Salvador, Hamed Khakzad, Benjamin Cocom-Chan, Charles Bou-Nader, Christophe Velours, Yosra Zarrouk, Christophe Le Clainche, Christian Malosse, Diogo Borges Lima, Nicole Quenech'Du, Bilal Mazhar, Sami Essid, Marc Fontecave, Atef Asnacios, Julia Chamot-Rooke, Lars Malmström, Guy Tran Van Nhieu
||Upon activation, vinculin reinforces cytoskeletal anchorage during cell adhesion. Activating ligands classically disrupt intramolecular interactions between the vinculin head and tail domains that bind to actin filaments. Here, we show that Shigella IpaA triggers major allosteric changes in the head domain, leading to vinculin homo-oligomerization. Through the cooperative binding of its three vinculin-binding sites (VBSs), IpaA induces a striking reorientation of the D1 and D2 head subdomains associated with vinculin oligomerization. IpaA thus acts as a catalyst producing vinculin clusters that bundle actin at a distance from the activation site and trigger the formation of highly stable adhesions resisting the action of actin relaxing drugs. Unlike canonical activation, vinculin homo-oligomers induced by IpaA appear to keep a persistent imprint of the activated state in addition to their bundling activity, accounting for stable cell adhesion independent of force transduction and relevant to bacterial invasion.