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

Autor(es)

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]

Afiliação do(s) autor(es):Mostrar menos -

^[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

• Tipo de documento: Artigo Científico
• Fonte: SCIENCE ADVANCES; v. 6, n. 33 AUG 2020.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 10/17662-8 - Ressonância magnética eletrônica em estudos de estrutura, função e interações de moléculas com interesse biológico
• Beneficiário: Antonio José da Costa Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/20358-4 - Interações moleculares no mecanismo de ação da proteína P7 do vírus da Hepatite C e da galectina-4 humana
• Beneficiário: Patricia Suemy Kumagai
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 11/21767-2 - Interações moleculares no mecanismo de ação da galectina-4 humana
• Beneficiário: Patricia Suemy Kumagai
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto