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ipaA triggers vinculin oligomerization to strengthen cell adhesion during Shigella invasion

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Atef Asnacios

Abstract

The Shigella effector IpaA co-opts the focal adhesion protein vinculin to promote bacterial invasion. Here, we show that IpaA triggers an unreported mode of vinculin activation through the cooperative binding of its three vinculin-binding sites (VBSs) leading to vinculin oligomerization via its D1 and D2 head subdomains and highly stable adhesions resisting actin relaxing drugs. Using cross-linking mass spectrometry, we found that while IpaA VBSs1-2 bound to D1, IpaA VBS3 interacted with D2, a subdomain masked to other known VBSs. Structural modeling indicated that as opposed to canonical activation linked to interaction with D1, these combined VBSs interactions triggered major allosteric changes leading to D1D2 oligomerization. A cysteine-clamp preventing these changes and D1D2 oligomerization impaired growth of vinculin microclusters and cell adhesion. We propose that D1D2-mediated vinculin oligomerization occurs during the maturation of adhesion structures to enable the scaffolding of high-order vinculin complexes, and is triggered by Shigella IpaA to promote bacterial invasion in the absence of mechanotransduction.

Dates and versions

inserm-03165086 , version 1 (10-03-2021)

Licence

Attribution - NonCommercial - NoDerivatives - CC BY 4.0

Identifiers

Cite

Cesar Valencia-Gallardo, Daniel-Isui Aguilar-Salvador, Hamed Khakzad, Charles Bou-Nader, Christian Malosse, et al.. ipaA triggers vinculin oligomerization to strengthen cell adhesion during Shigella invasion. 2021. ⟨inserm-03165086⟩
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