TCB Publications - Abstract

Ksenia Terekhova, Sabine Pokutta, Yee S. Kee, Jing Li, Emad Tajkhorshid, Gerald Fuller, Alexander R. Dunn, and William I. Weis. Binding partner- and force-promoted changes in αE-catenin conformation probed by native cysteine labeling. Scientific Reports, 9:15375, 2019. (PMC: PMC6814714)

TERE2019-ET Adherens Junctions (AJs) are cell-cell adhesion complexes that sense and propagate mechanical forces by coupling cadherins to the actin cytoskeleton via $\beta$-catenin and the F-actin binding protein $\alpha$E-catenin. When subjected to mechanical force, the cadherin$\cdot$catenin complex can tightly link to F-actin through $\alpha$E-catenin, and also recruits the F-actin-binding protein vinculin. In this study, labeling of native cysteines combined with mass spectrometry revealed conformational changes in $\alpha$E-catenin upon binding to the E-cadherin$\cdot \beta$-catenin complex, vinculin and F-actin. A method to apply physiologically meaningful forces in solution revealed force-induced conformational changes in $\alpha$E-catenin when bound to F-actin. Comparisons of wild-type $\alpha$E- catenin and a mutant with enhanced vinculin affinity using cysteine labeling and isothermal titration calorimetry provide evidence for allosteric coupling of the N-terminal $\beta$-catenin-binding and the middle (M) vinculin-binding domain of $\alpha$E-catenin. Cysteine labeling also revealed possible crosstalk between the actin-binding domain and the rest of the protein. The data provide insight into how binding partners and mechanical stress can regulate the conformation of full-length $\alpha$E-catenin, and identify the M domain as a key transmitter of conformational changes.

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