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| Title | Afadin mediates cadherin-catenin complex clustering on F-actin linked to cooperative binding and filament curvature. |
|---|---|
| Journal, issue, pages | bioRxiv, Year 2024 |
| Publish date | Oct 11, 2024 |
Authors | Rui Gong / Matthew J Reynolds / Xiaoyu Sun / Gregory M Alushin / ![]() |
| PubMed Abstract | The E-cadherin-β-catenin-αE-catenin (cadherin-catenin) complex couples the cytoskeletons of neighboring cells at adherens junctions (AJs) to mediate force transmission across epithelia. Mechanical ...The E-cadherin-β-catenin-αE-catenin (cadherin-catenin) complex couples the cytoskeletons of neighboring cells at adherens junctions (AJs) to mediate force transmission across epithelia. Mechanical force and auxiliary binding partners converge to stabilize the cadherin-catenin complex's inherently weak binding to actin filaments (F-actin) through unclear mechanisms. Here we show that afadin's coiled-coil (CC) domain and vinculin synergistically enhance the cadherin-catenin complex's F-actin engagement. The cryo-EM structure of an E-cadherin-β-catenin-αE-catenin-vinculin-afadin-CC supra-complex bound to F-actin reveals that afadin-CC bridges adjacent αE-catenin actin-binding domains along the filament, stabilizing flexible αE-catenin segments implicated in mechanical regulation. These cooperative binding contacts promote the formation of supra-complex clusters along F-actin. Additionally, cryo-EM variability analysis links supra-complex binding along individual F-actin strands to nanoscale filament curvature, a deformation mode associated with cytoskeletal forces. Collectively, this work elucidates a mechanistic framework by which vinculin and afadin tune cadherin-catenin complex-cytoskeleton coupling to support AJ function across varying mechanical regimes. |
External links | bioRxiv / PubMed:39415991 / PubMed Central |
| Methods | EM (single particle) / EM (tomography) |
| Resolution | 3.1 - 4.7 Å |
| Structure data | EMDB-47194, PDB-9dva: ![]() EMDB-47195: Alpha-E-catenin ABD (cadherin-catenin complex) and afadin bound to bent F-actin ![]() EMDB-47196: Cryo-EM structure of bare F-actin ![]() EMDB-47197: Alpha-E-catenin ABD (cadherin-catenin complex) and afadin bound to straight F-actin ![]() EMDB-47198: Tomogram of the cadherin-catenin-vinculin-afadin complex bound to F-actin |
| Chemicals | ![]() ChemComp-ADP: ![]() ChemComp-MG: |
| Source |
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Keywords | STRUCTURAL PROTEIN / Cytoskeleton / cell adhesion |
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