Bush, MartinAlhanshali, Bashir MQian, ShuoStanley, Christopher BHeller, William TMatsui, TsutomuWeiss, Thomas MNicholl, Iain DWalz, ThomasCallaway, David JEBu, Zimei2019-11-062019-11-062019-10-07Bush, M., Alhanshali, B. M., Qian, S., Stanley, C. B., Heller, W. T., Matsui, T., Weiss, T. M., Nicholl, I. D., Walz, T., Callaway, D. J. E.and Bu, Z. (2019) An ensemble of flexible conformations underlies mechanotransduction by the cadherin-catenin adhesion complex, Proceedings of the National Academy of Sciences, 116(43), pp. 21545-21555.0027-842410.1073/pnas.1911489116http://hdl.handle.net/2436/622912© 2019 The Authors. Published by National Academy of Sciences. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1073/pnas.1911489116The cadherin–catenin adhesion complex is the central component of the cell–cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the α-catenin•β-catenin•epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible “tongue” that is inserted into α-catenin and participates in the assembly of the ABE complex. The unanticipated ensemble of flexible conformations of the ABE complex suggests a dynamic mechanism for sensitivity and reversibility when transducing mechanical signals, in addition to the catch/slip bond behavior displayed by the ABE complex under mechanical tension. Our results provide mechanistic insight into the structural dynamics for the cadherin–catenin adhesion complex in mechanotransduction.application/pdfenadherens junctionmechanotransductionnegative stain electron microscopysmall-angle X-ray scatteringsmall-angle neutron scatteringJournal article1091-6490Proceedings of the National Academy of Sciences2019-10-31