Modulation of the turkey β1-adrenergic receptor by membrane rafts: insight from molecular dynamics

Ghumman, Afshan; Robinson, David

Abstract

G-protein coupled receptors are targets for ~70% of drugs. These receptors are responsible for signal transduction within a cell membrane (and further into the cell) and disruption to this signaling cascade is responsible for several non-infectious diseases. Membrane rafts exhibit significantly altered properties in comparison to fluid bilayers and as such may regulate certain GPCR’s, or be responsible for errors in signaling. Using molecular dynamics, we have investigated the conformations of the turkey β1-adrenergic receptor with and without an agonist in sphingolipid and cholesterol rich bilayers, typical of raft compositions, and compared these to cholesterol-poor bilayers. We find that the raft-like lipid bilayers are responsible for significantly altering the conformation of the receptor, even when an agonist is present.

Citation

Ghumman, A., & Robinson, D. (in press). Modulation of the turkey β1-adrenergic receptor by membrane rafts: insight from molecular dynamics. ChemistrySelect, 1(14), https://doi.org/10.1002/slct.20160084

• Journal Article Type: Article
• Acceptance Date: Aug 30, 2016
• Online Publication Date: Sep 8, 2016
• Deposit Date: Sep 13, 2016
• Publicly Available Date: Sep 13, 2016
• Journal: ChemistrySelect
• Electronic ISSN: 2365-6549
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 1
• Issue: 14
• DOI: https://doi.org/10.1002/slct.20160084
• Public URL: https://nottingham-repository.worktribe.com/output/818629
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/slct.201600849/abstract;jsessionid=E2A11EE4B26662EF19BAFB412FC1E462.f01t03
• Additional Information: This is the peer reviewed version of the following article: A. Ghumman, D. Robinson, Modulation of the turkey ß1-adrenergic receptor by membrane rafts : insight from molecular dynamics. ChemistrySelect 2016, v. 1, no. 14, p. 4274–4276 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/slct.201600849/abstract;jsessionid=E2A11EE4B26662EF19BAFB412FC1E462.f01t03. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• Contract Date: Sep 13, 2016