title: Membrane-sensitive conformational states of helix 8 in the metabotropic Glu2 receptor, a class C GPCR.
abstract: The recent elucidation of the X-ray structure of several class A GPCRs clearly indicates that the amphipathic helix 8 (H8) is a conserved structural domain in most crystallized GPCRs. Very little is known about the presence and the possible role of an analogous H8 domain in the distantly related class C GPCRs. In this study, we investigated the structural properties for the H8 domain of the mGluR2 receptor, a class C GPCR, by applying extended molecular dynamics simulations. Our study indicates that the amphipathic H8 adopts membrane-sensitive conformational states, which depend on the membrane composition. Cholesterol-rich membranes stabilize the helical structure of H8 whereas cholesterol-depleted membranes induce a disruption of H8. The observed link between membrane cholesterol levels and H8 conformational states suggests that H8 behaves as a sensor of cholesterol concentration.
authors.affiliation: Computer-Assisted Drug Design Lab, Research Programme on Biomedical Informatics (GRIB), Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Agostino
authors.initials: A
authors.lastname: Bruno
authors.forename: Gabriele
authors.initials: G
authors.lastname: Costantino
authors.forename: Gianni
authors.initials: G
authors.lastname: de Fabritiis
authors.forename: Manuel
authors.initials: M
authors.lastname: Pastor
authors.forename: Jana
authors.initials: J
authors.lastname: Selent
mesh_terms: D002462:Cell Membrane / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D002784:Cholesterol