Cited by 58Lipid Membrane Structure and BehaviorReceptor Mechanisms and SignalingProtein Structure and Dynamics

Interplay of G Protein-Coupled Receptors with the Membrane: Insights from Supra-Atomic Coarse Grain Molecular Dynamics Simulations

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Periole, Xavier·2017·Chemical Reviews

Abstract

G protein-coupled receptors (GPCRs) are central to many fundamental cellular signaling pathways. They transduce signals from the outside to the inside of cells in physiological processes ranging from vision to immune response. It is extremely challenging to look at them individually using conventional experimental techniques. Recently, a pseudo atomistic molecular model has emerged as a valuable tool to access information on GPCRs, more specifically on their interactions with their environment in their native cell membrane and the consequences on their supramolecular organization. This approach uses the Martini coarse grain (CG) model to describe the receptors, lipids, and solvent in molecular dynamics (MD) simulations and in enough detail to allow conserving the chemical specificity of the different molecules. The elimination of unnecessary degrees of freedom has opened up large-scale simulations of the lipid-mediated supramolecular organization of GPCRs. Here, after introducing the Martini CGMD method, we review these studies carried out on various members of the GPCR family, including rhodopsin (visual receptor), opioid receptors, adrenergic receptors, adenosine receptors, dopamine receptor, and sphingosine 1-phosphate receptor. These studies have brought to light an interesting set of novel biophysical principles. The insights range from revealing localized and heterogeneous deformations of the membrane bilayer at the surface of the protein, specific interactions of lipid molecules with individual GPCRs, to the effect of the membrane matrix on global GPCR self-assembly. The review ends with an overview of the lessons learned from the use of the CGMD method, the biophysical-chemical findings on lipid-protein interplay.

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  1. [3](3) Kruse, A. C.; Hu, J.; Pan, A. C.; Arlow, D. H.; Rosenbaum, D. M.; Rosemond, E.; Green, H. F.; Liu, T.; Chae, P. S.; Dror, R. O.; et al. Structure and Dynamics of the M3Muscarinic Acetylcholine Receptor. Nature 2012 , 482 , 552 -556. -
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Cited by

Authors
Periole, X.
Affiliations
Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands
Venue
Chemical Reviews
Published
2016-11-29
Volume
117
Issue
1
Pages
156-185
ISSN
  • 0009-2665 (ISSN-L)
  • 1520-6890
OpenAlex
W2559129809
Cited by
58
References
239
Citations by year
2026: 5 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 15 · 2018: 7 · 2017: 11
FWCI
0.99
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Chemical Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
G protein-coupled receptors, Martini coarse-grained model, protein-lipid interactions, rhodopsin, opioid receptors, adrenergic receptors, adenosine receptors, dopamine receptors, sphingosine-1-phosphate receptor, supramolecular organization
MeSH terms
Cell Membrane, Receptors, G-Protein-Coupled, Molecular Dynamics Simulation

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