Membrane-sensitive conformational states of helix 8 in the metabotropic Glu2 receptor, a class C GPCR

Bruno, Agostino; Costantino, Gabriele; De Fabritiis, Gianni; Pastor Maeso, Manuel; Selent, Jana

doi:http://dx.doi.org/10.1371/journal.pone.0042023

Membrane-sensitive conformational states of helix 8 in the metabotropic Glu2 receptor, a class C GPCR

Citation

Bruno A, Costantino G, de Fabritiis G, Pastor M, Selent J. Membrane-sensitive conformational states of helix 8 in the metabotropic Glu2 receptor, a class C GPCR. PLoS ONE. 2012;7(8):e42023. DOI: 10.1371/journal.pone.0042023

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.