Nicholl, IainMatsui, TsutomuWeiss, Thomas MStanley, Christopher BHeller, William TMartel, AnneFarago, BelaCallaway, David JEBu, Zimei2018-10-042018-10-042018-07-11Nicholl, ID., Matsui, T., Weiss, TM., Stanley, CB., Heller, WT., Martel, A., Farago, B., Callaway, DJE., Bu, Z. (2018) 'α-Catenin Structure and Nanoscale Dynamics in Solution and in Complex with F-Actin', Biophysical Journal, 115 (4) pp. 642-654 doi: 10.1016/j.bpj.2018.07.0050006-349510.1016/j.bpj.2018.07.005http://hdl.handle.net/2436/621755As a core component of the adherens junction, α-catenin stabilizes the cadherin/catenin complexes to the actin cytoskeleton for the mechanical coupling of cell-cell adhesion. α-catenin also modulates actin dynamics, cell polarity, and cell-migration functions that are independent of the adherens junction. We have determined the solution structures of the α-catenin monomer and dimer using in-line size-exclusion chromatography small-angle X-ray scattering, as well as the structure of α-catenin dimer in complex to F-actin filament using selective deuteration and contrast-matching small angle neutron scattering. We further present the first observation, to our knowledge, of the nanoscale dynamics of α-catenin by neutron spin-echo spectroscopy, which explicitly reveals the mobile regions of α-catenin that are crucial for binding to F-actin. In solution, the α-catenin monomer is more expanded than either protomer shown in the crystal structure dimer, with the vinculin-binding M fragment and the actin-binding domain being able to adopt different configurations. The α-catenin dimer in solution is also significantly more expanded than the dimer crystal structure, with fewer interdomain and intersubunit contacts than the crystal structure. When in complex to F-actin, the α-catenin dimer has an even more open and extended conformation than in solution, with the actin-binding domain further separated from the main body of the dimer. The α-catenin-assembled F-actin bundle develops into an ordered filament packing arrangement at increasing α-catenin/F-actin molar ratios. Together, the structural and dynamic studies reveal that α-catenin possesses dynamic molecular conformations that prime this protein to function as a mechanosensor protein.enalpha-cateninF-actinSANSNSEJournal articleBiophysical Journal