Tools
ToolsMuñoz-García, Juan C., Dijkman, Patricia M., Lavington, Steven, Suemy Kumagai, Patricia, Inacio dos Reis, Rosana, Yin, Daniel, Stansfeld, Phillip J., Costa-Filho, Antonio José and Watts, Anthony (2020) Conformational dynamics of a G protein–coupled receptor helix 8 in lipid membranes. Science Advances, 6 (33). ISSN 2375-2548
Preview |
PDF (Published_Version)
- Published Version
Available under License Creative Commons Attribution Non-commercial. Download (1MB) | Preview |
Abstract
G protein–coupled receptors (GPCRs) are the largest and pharmaceutically most important class of membrane proteins encoded in the human genome, characterized by a seven-transmembrane helix architecture and a C-terminal amphipathic helix 8 (H8). In a minority of GPCR structures solved to date, H8 either is absent or adopts an unusual conformation. The controversial existence of H8 of the class A GPCR neurotensin receptor 1 (NTS1) has been examined here for the nonthermostabilized receptor in a functionally supporting membrane environment using electron paramagnetic resonance, molecular dynamics simulations, and circular dichroism. Lipid-protein interactions with phosphatidylserine and phosphatidylethanolamine lipids, in particular, stabilize the residues 374 to 390 of NTS1 into forming a helix. Furthermore, introduction of a helix-breaking proline residue in H8 elicited an increase in ß-arrestin–NTS1 interactions observed in pull-down assays, suggesting that the structure and/or dynamics of H8 might play an important role in GPCR signaling.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Science > School of Pharmacy |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 17 Aug 2020 23:55 |
| Last Modified: | 20 Apr 2023 17:34 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/76463 |
| DOI: | 10.1126/sciadv.aav8207 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |