ipaA triggers vinculin oligomerization to strengthen cell adhesion during Shigella invasion
Cesar Valencia-Gallardo
(1, 2)
,
Daniel-Isui Aguilar-Salvador
(1, 2)
,
Hamed Khakzad
(1, 3, 4)
,
Charles Bou-Nader
(5)
,
Christian Malosse
(6)
,
Diogo Borges Lima
(6)
,
Chakir Bello
(1, 2)
,
Benjamin Cocom-Chan
(1, 2)
,
Nicole Quenech’du
(1, 2)
,
Bilal Mazhar
(1, 2)
,
Delphine Javelaud
(7)
,
Jacques Fattaccioli
(8)
,
Alain Mauviel
(7)
,
Marc Fontecave
(5)
,
Atef Asnacios
(9)
,
Julia Chamot-Rooke
(6)
,
Lars Malmström
(3, 10, 4)
,
Guy Tran van Nhieu
(1, 2)
1
CIRB -
Centre interdisciplinaire de recherche en biologie
2 Labex MemoLife
3 SIB - Swiss Institute of Bioinformatics [Lausanne]
4 UZH - Universität Zürich [Zürich] = University of Zurich
5 LCPB - Laboratoire de Chimie des Processus Biologiques
6 UTechS MSBio - Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology
7 Signalisation, radiobiologie et cancer
8 PASTEUR - Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640)
9 MSC - Matière et Systèmes Complexes
10 Skane University Hospital [Lund]
2 Labex MemoLife
3 SIB - Swiss Institute of Bioinformatics [Lausanne]
4 UZH - Universität Zürich [Zürich] = University of Zurich
5 LCPB - Laboratoire de Chimie des Processus Biologiques
6 UTechS MSBio - Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology
7 Signalisation, radiobiologie et cancer
8 PASTEUR - Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640)
9 MSC - Matière et Systèmes Complexes
10 Skane University Hospital [Lund]
Hamed Khakzad
- Fonction : Auteur
- PersonId : 1304933
- IdHAL : hamedkhakzad
Jacques Fattaccioli
- Fonction : Auteur
- PersonId : 177876
- IdHAL : jacques-fattaccioli
- ORCID : 0000-0002-0095-2576
- IdRef : 116337222
Marc Fontecave
- Fonction : Auteur
- PersonId : 1145371
- ORCID : 0000-0002-8016-4747
- IdRef : 073952400
Atef Asnacios
- Fonction : Auteur
- PersonId : 1010956
- ORCID : 0000-0002-3146-476X
- IdRef : 095014373
Julia Chamot-Rooke
- Fonction : Auteur
- PersonId : 742132
- IdHAL : jchamot
- ORCID : 0000-0002-9427-543X
- IdRef : 119949687
Résumé
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.