Title:
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Membrane-sensitive conformational states of helix 8 in the metabotropic Glu2 receptor, a class C GPCR
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Author:
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Bruno, Agostino; Costantino, Gabriele; De Fabritiis, Gianni; Pastor Maeso, Manuel; Selent, Jana
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Abstract:
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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. |
Abstract:
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The authors gratefully acknowledge financial support from La MARATO de TV3 Foundation (Ref.-No. 091010) and the Spanish Ministerio de Educación y Ciencia (SAF2009-13609-C04-04). GC and AB gratefully acknowledge the CINECA consortium for the suppor |
Subject(s):
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-Membranes cel·lulars -Colesterol -- Metabolisme |
Rights:
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© 2012 Bruno et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits/nunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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Document type:
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Article Article - Published version |
Published by:
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Public Library of Science (PLoS)
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