James R. Lloyd
Mapping the interaction between eukaryotic initiation factor 4A (eIF4A) and the inhibitor hippuristanol using carbene footprinting and mass spectrometry
Lloyd, James R.; Hogan, Amy; Paschalis, Vasileios; Bellamy-Carter, Jeddidiah; Bottley, Andrew; Seymour, Graham B.; Hayes, Christopher J.; Oldham, Neil J.
Authors
Amy Hogan
Vasileios Paschalis
Jeddidiah Bellamy-Carter
Andrew Bottley
Graham B. Seymour
Professor CHRIS HAYES chris.hayes@nottingham.ac.uk
PROFESSOR OF ORGANIC CHEMISTRY
Professor NEIL OLDHAM NEIL.OLDHAM@NOTTINGHAM.AC.UK
PROFESSOR OF BIOMOLECULAR SPECTROMETRY
Abstract
Protein-ligand interactions are central to protein activity and cell functionality. Improved knowledge of these relationships greatly benefits our understanding of key biological processes and aids in rational drug design towards the treatment of clinically relevant diseases. Carbene footprinting is a recently developed mass spectrometry-based chemical labelling technique that provides valuable information relating to protein-ligand interactions, such as the mapping of binding sites and associated conformational change. Here, we show the application of carbene footprinting to the interaction between eIF4A helicase and a natural product inhibitor, hippuristanol, found in the coral Isis hippuris. Upon addition of hippuristanol we identified reduced carbene labelling (masking) in regions of eIF4A previously implicated in ligand binding. Additionally, we detected hippuristanol-associated increased carbene labelling (unmasking) around the flexible hinge region of eIF4A, indicating ligand-induced conformational change. This work represents further development of the carbene footprinting technique and demonstrates its potential in characterising medicinally relevant protein-ligand interactions.
Citation
Lloyd, J. R., Hogan, A., Paschalis, V., Bellamy-Carter, J., Bottley, A., Seymour, G. B., Hayes, C. J., & Oldham, N. J. (2021). Mapping the interaction between eukaryotic initiation factor 4A (eIF4A) and the inhibitor hippuristanol using carbene footprinting and mass spectrometry. Proteomics, 21(21-22), Article 2000288. https://doi.org/10.1002/pmic.202000288
Journal Article Type | Article |
---|---|
Acceptance Date | May 17, 2021 |
Online Publication Date | May 24, 2021 |
Publication Date | 2021-11 |
Deposit Date | Jun 1, 2021 |
Publicly Available Date | May 25, 2022 |
Journal | Proteomics |
Print ISSN | 1615-9853 |
Electronic ISSN | 1615-9861 |
Publisher | Wiley |
Peer Reviewed | Peer Reviewed |
Volume | 21 |
Issue | 21-22 |
Article Number | 2000288 |
DOI | https://doi.org/10.1002/pmic.202000288 |
Keywords | Biochemistry; Molecular Biology |
Public URL | https://nottingham-repository.worktribe.com/output/5619680 |
Publisher URL | https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/pmic.202000288 |
Additional Information | This is the peer reviewed version of the following article: Lloyd, J. R., Hogan, A., Paschalis, V., Bellamy-Carter, J., Bottley, A., Seymour, G. B., Hayes, C. J., & Oldham, N. J. (2021). Mapping the interaction between eukaryotic initiation factor 4A (eIF4A) and the inhibitor hippuristanol using carbene footprinting and mass spectrometry. Proteomics. e2000288, which has been published in final form at https://doi.org/10.1002/pmic.202000288. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. |
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