Résumé

The μ opioid receptor (μOR), which is part of the G protein-coupled receptors family, is a membrane protein that is modulated by its lipid environment. In the present work, we model μOR in three different membrane systems: POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine), and DPPC (1, 2-dipalmitoyl-sn-glycero-3-phosphocholine) through 45 μs molecular dynamics (MD) simulations at the coarse-grained level. Our theoretical studies provide new insights to the lipid-induced modulation of the receptor. Particularly, to characterize how μOR interacts with each lipid, we analyze the tilt of the protein, the number of contacts occurring between the lipids and each amino acid of the receptor, and the μOR-lipid interface described as a network graph. We also analyze the variations in the number and the nature of the protein contacts that are induced by the lipid structure. We show that POPC interacts preferentially
with helix 1 (H1) and helices H5-H6, POPE, with H5-H6 and H6-H7, and DPPC, with H4 and
H6. We demonstrate how each of the three lipids shape the structure of the μOR.
langue originaleAnglais
Numéro d'articlee0213646
Nombre de pages19
journalPLoS ONE
étatPublié - 2019

Empreinte digitale

molecular dynamics
narcotics
Opioid Receptors
Molecular Dynamics Simulation
Molecular dynamics
Lipids
receptors
lipids
Amino Acid Receptors
G-Protein-Coupled Receptors
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine
1-palmitoyl-2-oleoylphosphatidylcholine
colfosceril palmitate
phosphorylethanolamine
membrane proteins
Membrane Proteins
Proteins
Theoretical Models
proteins
Modulation

Citer ceci

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title = "Interaction of POPC, DPPC, and POPE with the μ opioid receptor: A coarse-grained molecular dynamics study",
abstract = "The μ opioid receptor (μOR), which is part of the G protein-coupled receptors family, is a membrane protein that is modulated by its lipid environment. In the present work, we model μOR in three different membrane systems: POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine), and DPPC (1, 2-dipalmitoyl-sn-glycero-3-phosphocholine) through 45 μs molecular dynamics (MD) simulations at the coarse-grained level. Our theoretical studies provide new insights to the lipid-induced modulation of the receptor. Particularly, to characterize how μOR interacts with each lipid, we analyze the tilt of the protein, the number of contacts occurring between the lipids and each amino acid of the receptor, and the μOR-lipid interface described as a network graph. We also analyze the variations in the number and the nature of the protein contacts that are induced by the lipid structure. We show that POPC interacts preferentiallywith helix 1 (H1) and helices H5-H6, POPE, with H5-H6 and H6-H7, and DPPC, with H4 andH6. We demonstrate how each of the three lipids shape the structure of the μOR.",
author = "M-A Angladon and Mathieu Foss{\'e}pr{\'e} and Laurence Leherte and Daniel Vercauteren",
year = "2019",
language = "English",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",

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TY - JOUR

T1 - Interaction of POPC, DPPC, and POPE with the μ opioid receptor

T2 - A coarse-grained molecular dynamics study

AU - Angladon, M-A

AU - Fossépré, Mathieu

AU - Leherte, Laurence

AU - Vercauteren, Daniel

PY - 2019

Y1 - 2019

N2 - The μ opioid receptor (μOR), which is part of the G protein-coupled receptors family, is a membrane protein that is modulated by its lipid environment. In the present work, we model μOR in three different membrane systems: POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine), and DPPC (1, 2-dipalmitoyl-sn-glycero-3-phosphocholine) through 45 μs molecular dynamics (MD) simulations at the coarse-grained level. Our theoretical studies provide new insights to the lipid-induced modulation of the receptor. Particularly, to characterize how μOR interacts with each lipid, we analyze the tilt of the protein, the number of contacts occurring between the lipids and each amino acid of the receptor, and the μOR-lipid interface described as a network graph. We also analyze the variations in the number and the nature of the protein contacts that are induced by the lipid structure. We show that POPC interacts preferentiallywith helix 1 (H1) and helices H5-H6, POPE, with H5-H6 and H6-H7, and DPPC, with H4 andH6. We demonstrate how each of the three lipids shape the structure of the μOR.

AB - The μ opioid receptor (μOR), which is part of the G protein-coupled receptors family, is a membrane protein that is modulated by its lipid environment. In the present work, we model μOR in three different membrane systems: POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine), and DPPC (1, 2-dipalmitoyl-sn-glycero-3-phosphocholine) through 45 μs molecular dynamics (MD) simulations at the coarse-grained level. Our theoretical studies provide new insights to the lipid-induced modulation of the receptor. Particularly, to characterize how μOR interacts with each lipid, we analyze the tilt of the protein, the number of contacts occurring between the lipids and each amino acid of the receptor, and the μOR-lipid interface described as a network graph. We also analyze the variations in the number and the nature of the protein contacts that are induced by the lipid structure. We show that POPC interacts preferentiallywith helix 1 (H1) and helices H5-H6, POPE, with H5-H6 and H6-H7, and DPPC, with H4 andH6. We demonstrate how each of the three lipids shape the structure of the μOR.

UR - https://doi.org/10.1371/journal. pone.021364

M3 - Article

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

M1 - e0213646

ER -