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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Conformational dynamics of a G protein-coupled receptor helix 8 in lipid membranes

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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:
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[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)