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

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  • dc.contributor.author Bruno, Agostinoca
  • dc.contributor.author Costantino, Gabrieleca
  • dc.contributor.author De Fabritiis, Giannica
  • dc.contributor.author Pastor Maeso, Manuelca
  • dc.contributor.author Selent, Janaca
  • dc.date.accessioned 2015-05-12T09:47:01Z
  • dc.date.available 2015-05-12T09:47:01Z
  • dc.date.issued 2012ca
  • dc.description.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.en
  • dc.description.sponsorship 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 supporen
  • dc.format.mimetype application/pdfca
  • dc.identifier.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.0042023ca
  • dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0042023
  • dc.identifier.issn 1932-6203ca
  • dc.identifier.uri http://hdl.handle.net/10230/23556
  • dc.language.iso engca
  • dc.publisher Public Library of Science (PLoS)ca
  • dc.relation.ispartof PLoS ONE. 2012;7(8):e42023
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2009-13609
  • dc.rights © 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 crediteden
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.subject.other Membranes cel·lularsca
  • dc.subject.other Colesterol -- Metabolismeca
  • dc.title Membrane-sensitive conformational states of helix 8 in the metabotropic Glu2 receptor, a class C GPCRen
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca