Vagrys, Darius, Davidson, James, Chen, Ijen et al. (2 more authors) (2020) Exploring idp–ligand interactions:Tau k18 as a test case. International Journal of Molecular Sciences. 5257. ISSN 1422-0067
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 by the authors. |
Keywords: | Intrinsically disordered protein,Microscale thermophoresis,Nuclear magnetic resonance,Surface plasmon resonance,Tau K18 |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Funding Information: | Funder Grant number EUROPEAN COMMISSION 675899 |
Depositing User: | Pure (York) |
Date Deposited: | 05 Aug 2020 08:40 |
Last Modified: | 16 Oct 2024 16:51 |
Published Version: | https://doi.org/10.3390/ijms21155257 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.3390/ijms21155257 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:164050 |
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Filename: ijms_21_05257_v2.pdf
Description: Exploring IDP–Ligand Interactions: Tau K18 as a Test Case
Licence: CC-BY 2.5