An ensemble of flexible conformations underlies mechanotransduction by the cadherin-catenin adhesion complex
Alhanshali, Bashir M
Stanley, Christopher B
Heller, William T
Weiss, Thomas M
Nicholl, Iain D
Callaway, David JE
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AbstractThe 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.
CitationBush, 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.
JournalProceedings of the National Academy of Sciences
Description© 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.1911489116
SponsorsThis research was funded by NSF Grant MCB-1817684 (to Z.B.) and National Center for Research Resources Grant 2G12 RR003060 (to City College of New York). A portion of the research conducted at Oak Ridge National Laboratory’s Spallation Neutron Source and High Flux Isotope Reactor was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy (DOE). The Bio-SANS of the Center for Structural Molecular Biology at the High Flux Isotope Reactor is supported by the Office of Biological and Environmental Research of the DOE. Use of the SSRL, Stanford Linear Accelerator Center’s is supported by DOE, Office of Science, Office of Basic Energy Sciences Contract DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and NIH, National Institute of General Medical Sciences (NIGMS) Grant P41 GM103393.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/