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TitleMolecular mechanism for direct actin force-sensing by α-catenin.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateSep 24, 2020
AuthorsLin Mei / Santiago Espinosa de Los Reyes / Matthew J Reynolds / Rachel Leicher / Shixin Liu / Gregory M Alushin /
PubMed AbstractThe actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force; however, it is unclear ...The actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force; however, it is unclear how interactions between actin filaments (F-actin) and associated proteins are mechanically regulated. Here we employ both optical trapping and biochemical reconstitution with myosin motor proteins to show single piconewton forces applied solely to F-actin enhance binding by the human version of the essential cell-cell adhesion protein αE-catenin but not its homolog vinculin. Cryo-electron microscopy structures of both proteins bound to F-actin reveal unique rearrangements that facilitate their flexible C-termini refolding to engage distinct interfaces. Truncating α-catenin's C-terminus eliminates force-activated F-actin binding, and addition of this motif to vinculin confers force-activated binding, demonstrating that α-catenin's C-terminus is a modular detector of F-actin tension. Our studies establish that piconewton force on F-actin can enhance partner binding, which we propose mechanically regulates cellular adhesion through α-catenin.
External linksElife / PubMed:32969337 / PubMed Central
MethodsEM (helical sym.)
Resolution2.9 - 3.2 Å
Structure data

EMDB-20843, PDB-6upv:
Alpha-E-catenin ABD-F-actin complex
Method: EM (helical sym.) / Resolution: 3.2 Å

EMDB-20844, PDB-6upw:
Metavinculin ABD-F-actin complex
Method: EM (helical sym.) / Resolution: 2.9 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
  • Chicken (chicken)
  • gallus gallus (chicken)
KeywordsCELL ADHESION / alpha-catenin / catenin / actin / mechanobiology / mechanosensing / cytoskeleton / vinculin / metavinculin / focal adhesion

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