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Publication Abstract from PubMed

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 alphaE-catenin. When subjected to mechanical force, the cadherin*catenin complex can tightly link to F-actin through alphaE-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 alphaE-catenin upon binding to the E-cadherin*beta-catenin complex, vinculin and F-actin. A method to apply physiologically meaningful forces in solution revealed force-induced conformational changes in alphaE-catenin when bound to F-actin. Comparisons of wild-type alphaE-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 alphaE-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 alphaE-catenin, and identify the M domain as a key transmitter of conformational changes.

Binding partner- and force-promoted changes in alphaE-catenin conformation probed by native cysteine labeling.,Terekhova K, Pokutta S, Kee YS, Li J, Tajkhorshid E, Fuller G, Dunn AR, Weis WI Sci Rep. 2019 Oct 25;9(1):15375. doi: 10.1038/s41598-019-51816-3. PMID:31653927^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.