@article{98db1361a2884e36aae1c209128e1df4,
title = "Diffusion of a disordered protein on its folded ligand",
abstract = "Intrinsically disordered proteins often form dynamic complexes with their ligands. Yet, the speed and amplitude of these motions are hidden in classical binding kinetics. Here, we directly measure the dynamics in an exceptionally mobile, high-affinity complex. We show that the disordered tail of the cell adhesion protein E-cadherin dynamically samples a large surface area of the protooncogene β-catenin. Single-molecule experiments and molecular simulations resolve these motions with high resolution in space and time. Contacts break and form within hundreds of microseconds without a dissociation of the complex. The energy landscape of this complex is rugged with many small barriers (3 to 4 kBT) and reconciles specificity, high affinity, and extreme disorder. A few persistent contacts provide specificity, whereas unspecific interactions boost affinity.",
keywords = "Fuzzy complex, IDP, Molecular simulation, Protein dynamics, Single-molecule FRET",
author = "Felix Wiggers and Samuel Wohl and Artem Dubovetskyi and Gabriel Rosenblum and Wenwei Zheng and Hagen Hofmann",
note = "Funding Information: ACKNOWLEDGMENTS. We thank William I. Weis for providing the E-cad plasmid and for his helpful comments on the manuscript. We are also grateful to Dirk G{\"o}rlich for the plasmid containing the SUMO protease. Our thanks also go to Nir London and Christian Dubiella for their help with mass spectrometry. In addition, we enjoyed critical discussions with Gilad Haran, Amnon Horovitz, Koby Levy, Benjamin Schuler, Robert Best, and Philipp Selenko. This work was supported by the Israel Science Foundation (Grant No. 1549/15), the Benoziyo Fund for the Advancement of Science, the Carolito Foundation, the Leir Charitable Foundation, and the Koshland family. W.Z. acknowledges the support from the NSF (Grant MCB-2015030) and the research computing at Arizona State University for providing high performance computing. Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved.",
year = "2021",
month = sep,
day = "14",
doi = "10.1073/pnas.2106690118",
language = "English (US)",
volume = "118",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "37",
}