Diffusion of a disordered protein on its folded ligand
Felix Wiggers, Samuel Wohl, Artem Dubovetskyi, Gabriel Rosenblum, Wenwei Zheng, Hagen Hofmann
Abstract
Significance Flexibility in complexes between intrinsically disordered proteins and folded ligands is widespread in nature. However, timescales and spatial amplitudes of such dynamics remained unexplored for most systems. Our results show that the disordered cytoplasmic tail of the cell adhesion protein E-cadherin diffuses across the entire surface of its folded binding partner β-catenin at fast submillisecond timescales. The nanometer amplitude of these motions could allow kinases to access their recognition motifs without requiring a dissociation of the complex. We expect that the rugged energy landscape found in the E-cadherin/β-catenin complex is a defining feature of dynamic and partially disordered protein complexes.