title: Dissimilar interaction of CB1/CB2 with lipid bilayers as revealed by molecular dynamics simulation.
abstract: Cannabinoid receptors CB1 and CB2 are a striking class of transmembrane proteins involved in a high number of important biological processes. In spite of the inherent similarity (40% in aminoacid sequence) these receptors are found in different cell environments. In addition to this, CB1 activity has been intimately associated with lipid rafts whereas CB2 has not. In this work we have performed a 50 nanosecond molecular dynamics simulation of the inactive conformations of both receptors inserted in a POPC lipid bilayer. Although in both cases the overall protein structure is maintained along the entire simulation we have found important differences in the protein-lipid interaction. While CB1 tends to distort the lipid bilayer regularity, especially in the extracellular moiety, CB2 has a minor influence on the lipid distribution along the plane of the bilayer. This observation is consistent with some experimental facts observed in these cannabinoid receptors with regard to lipid/protein interaction.
authors.affiliation: GEMPPO, Departamento de Física Macromolecular, Instituto de Estructura de la Materia, CSIC, Serrano 113bis, 28006, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ramos
authors.forename: Víctor L
authors.initials: VL
authors.lastname: Cruz
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Salazar
authors.forename: Nuria E
authors.initials: NE
authors.lastname: Campillo
authors.forename: Juan A
authors.initials: JA
authors.lastname: Páez
mesh_terms: D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C028694:1-palmitoyl-2-oleoylphosphatidylcholine