The recent elucidation of the x-ray structure of several class A GPCRs has clearly indicated 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
Membrane-Sensitive Conformational States of Helix 8 in the Metabotropic Glu2 Receptor, a Class C GPCR / A., Bruno; Costantino, Gabriele; G., De Fabritis; M., Pastor; J., Salent. - In: PLOS ONE. - ISSN 1932-6203. - (2012). [10.1371/journal.pone.0042023]
Membrane-Sensitive Conformational States of Helix 8 in the Metabotropic Glu2 Receptor, a Class C GPCR
COSTANTINO, Gabriele;
2012-01-01
Abstract
The recent elucidation of the x-ray structure of several class A GPCRs has clearly indicated 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 concentrationI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
