Conformational dynamics of a G protein–coupled receptor helix 8 in lipid membranes
2020 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Conformational dynamics of a G protein–coupled receptor helix 8 in lipid membranes
Dijkman, P. M.; Muñoz-García, J. C.; Lavington, S. R.; Kumagai, P. S.; dos Reis, R. I.; Yin, D. & Stansfeld, P. J. et al. (2020)
Science Advances, 6(33) pp. eaav8207. DOI: https://doi.org/10.1126/sciadv.aav8207
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Details
- Authors
- Dijkman, Patricia M.; Muñoz-García, Juan C.; Lavington, Steven R.; Kumagai, Patricia Suemy; dos Reis, Rosana I.; Yin, Daniel; Stansfeld, Phillip J.; Costa-Filho, Antonio José; Watts, Anthony
- 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.
- Issue Date
- 2020
- Journal
- Science Advances
- Project
- EXC 2067: Multiscale Bioimaging
- Working Group
- RG Fernández-Busnadiego (Structural Cell Biology)
- eISSN
- 2375-2548
- Language
- English