| Full text | |
| Author(s): |
Dijkman, Patricia M.
[1, 2, 3, 4]
;
Munoz-Garcia, Juan C.
[1, 5]
;
Lavington, Steven R.
[1]
;
Kumagai, Patricia Suemy
[6, 1]
;
dos Reis, I, Rosana
;
Yin, Daniel
[7]
;
Stansfeld, Phillip J.
[8, 9, 10]
;
Costa-Filho, Antonio Jose
[11]
;
Watts, Anthony
[7]
Total Authors: 9
|
| Affiliation: Show less - | [1] Univ Oxford, Dept Biochem, Biomembrane Struct Unit, South Parks Rd, Oxford OX1 3QU - England
[2] Max Planck Inst Biophys, Max von Laue Str 3, D-60438 Frankfurt - Germany
[3] Univ Med Ctr Gottingen, Inst Neuropathol, Robert Koch Str 40, D-37075 Gottingen - Germany
[4] Univ Gottingen, Cluster Excellence Multiscale Bioimaging Mol Mach, Robert Koch Str 40, D-37075 Gottingen - Germany
[5] Univ East Anglia, Sch Pharm, Norwich Res Pk, Norwich NR4 7TJ, Norfolk - England
[6] Univ Sao Paulo, Inst Fis Sao Carlos, Av Trabalhador Sao Carlense 400, CP 369, BR-13560970 Sao Carlos, SP - Brazil
[7] dos Reis, Rosana, I, Univ Oxford, Dept Biochem, Biomembrane Struct Unit, South Parks Rd, Oxford OX1 3QU - England
[8] Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands - England
[9] Univ Oxford, Dept Biochem, South Parks Rd, Oxford OX1 3QU - England
[10] Univ Warwick, Sch Life Sci, Coventry CV4 7AL, W Midlands - England
[11] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Fis, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil
Total Affiliations: 11
|
| Document type: | Journal article |
| Source: | SCIENCE ADVANCES; v. 6, n. 33 AUG 2020. |
| Web of Science Citations: | 0 |
| 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 beta-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. (AU) | |
| FAPESP's process: | 10/17662-8 - Electron magnetic resonance in studies of structure, function and interactions of biologically-relevant molecules |
| Grantee: | Antonio José da Costa Filho |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 12/20358-4 - Molecular interactions in the mechanism of action of P7 protein from the Hepatitis C virus and of human galectin 4 |
| Grantee: | Patricia Suemy Kumagai |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate (Direct) |
| FAPESP's process: | 11/21767-2 - Molecular interactions in the mechanism of action of human galectin-4 |
| Grantee: | Patricia Suemy Kumagai |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |