Diffusion of a disordered protein on its folded ligand

Felix Wiggers, Samuel Wohl, Artem Dubovetskyi, Gabriel Rosenblum, Wenwei Zheng, Hagen Hofmann

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article numbere2106690118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number37
DOIs
StatePublished - Sep 14 2021

Keywords

  • Fuzzy complex
  • IDP
  • Molecular simulation
  • Protein dynamics
  • Single-molecule FRET

ASJC Scopus subject areas

  • General

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