Polymer effects modulate binding affinities in disordered proteins

Renee Vancraenenbroeck, Yair S. Harel, Wenwei Zheng, Hagen Hofmann

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Structural disorder is widespread in regulatory protein networks. Weak and transient interactions render disordered proteins particularly sensitive to fluctuations in solution conditions such as ion and crowder concentrations. How this sensitivity alters folding coupled binding reactions, however, has not been fully understood. Here, we demonstrate that salt jointly modulates polymer properties and binding affinities of 5 disordered proteins from a transcription factor network. A combination of single-molecule Förster resonance energy transfer experiments, polymer theory, and molecular simulations shows that all 5 proteins expand with increasing ionic strengths due to Debye-Hückel charge screening. Simultaneously, pairwise affinities between the proteins increase by an order of magnitude within physiological salt limits. A quantitative analysis shows that 50% of the affinity increase can be explained by changes in the disordered state. Disordered state properties therefore have a functional relevance even if these states are not directly involved in biological functions. Numerical solutions of coupled binding equilibria with our results show that networks of homologous disordered proteins can function surprisingly robustly in fluctuating cellular environments, despite the sensitivity of its individual proteins.

Original languageEnglish (US)
Pages (from-to)19506-19512
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number39
DOIs
StatePublished - Sep 24 2019
Externally publishedYes

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Polymers
Proteins
Salts
Energy Transfer
Osmolar Concentration
Transcription Factors
Ions

Keywords

  • Collapse
  • Intrinsically disordered protein
  • Protein folding
  • Protein network
  • Single-molecule FRET

ASJC Scopus subject areas

  • General

Cite this

Polymer effects modulate binding affinities in disordered proteins. / Vancraenenbroeck, Renee; Harel, Yair S.; Zheng, Wenwei; Hofmann, Hagen.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 39, 24.09.2019, p. 19506-19512.

Research output: Contribution to journalArticle

Vancraenenbroeck, Renee ; Harel, Yair S. ; Zheng, Wenwei ; Hofmann, Hagen. / Polymer effects modulate binding affinities in disordered proteins. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 39. pp. 19506-19512.
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