Exploring idp–ligand interactions: Tau k18 as a test case

Darius Vagrys, James Davidson, Ijen Chen, Roderick E. Hubbard, Ben Davis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Over the past decade intrinsically disordered proteins (IDPs) have emerged as a biologically important class of proteins, many of which are of therapeutic relevance. Here, we investigated the interactions between a model IDP system, tau K18, and nine literature compounds that have been reported as having an effect on tau in order to identify a robust IDP–ligand system for the optimization of a range of biophysical methods. We used NMR, surface plasmon resonance (SPR) and microscale thermophoresis (MST) methods to investigate the binding of these compounds to tau K18; only one showed unambiguous interaction with tau K18. Several near neighbors of this compound were synthesized and their interactions with tau K18 characterized using additional NMR methods, including 1D ligand-observed NMR, diffusion-ordered spectroscopy (DOSY) and19F NMR. This study demonstrates that it is possible to detect and characterize IDP–ligand interactions using biophysical methods. However, care must be taken to account for possible artefacts, particularly the impact of compound solubility and where the protein has to be immobilized.

Original languageEnglish
Article number5257
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number15
DOIs
Publication statusPublished - 24 Jul 2020

Bibliographical note

© 2020 by the authors.

Keywords

  • Intrinsically disordered protein
  • Microscale thermophoresis
  • Nuclear magnetic resonance
  • Surface plasmon resonance
  • Tau K18

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