Induced effects of sodium ions on dopaminergic G-protein coupled receptors

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• dc.contributor.author Selent, Janaca
• dc.contributor.author Sanz, Ferranca
• dc.contributor.author Pastor Maeso, Manuelca
• dc.contributor.author De Fabritiis, Giannica
• dc.date.accessioned 2015-04-17T07:07:37Z
• dc.date.available 2015-04-17T07:07:37Z
• dc.date.issued 2010ca
• dc.description.abstract G-protein coupled receptors, the largest family of proteins in the human genome, are involved in many complex signal transduction pathways, typically activated by orthosteric ligand binding and subject to allosteric modulation. Dopaminergic receptors, belonging to the class A family of G-protein coupled receptors, are known to be modulated by sodium ions from an allosteric binding site, although the details of sodium effects on the receptor have not yet been described. In an effort to understand these effects, we performed microsecond scale all-atom molecular dynamics simulations on the dopaminergic D2 receptor, finding that sodium ions enter the receptor from the extracellular side and bind at a deep allosteric site (Asp2.50). Remarkably, the presence of a sodium ion at this allosteric site induces a conformational change of the rotamer toggle switch Trp6.48 which locks in a conformation identical to the one found in the partially inactive state of the crystallized human β2 adrenergic receptor. This study provides detailed quantitative information about binding of sodium ions in the D2 receptor and reports a possibly important sodium-induced conformational change for modulation of D2 receptor function.en
• dc.description.sponsorship We acknowledge partial support from the EU funded VPH Network of Excellence, La MARATO de TV3 Foundation (Ref.-No. 091010), the HERACLES (RD06/0009) and COMBIOMED (RD07/0067), the Spanish Ministerio de Educacion y Ciencia (SAF2009-13609-C04-04). GDF acknowledges support from the Ramon y Cajal scheme and by the Spanish Ministry of Science and Innovation (Ref. FIS2008-01040). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripten
• dc.format.mimetype application/pdfca
• dc.identifier.citation Selent J, Sanz F, Pastor M, de Fabritiis G. Induced effects of sodium ions on dopaminergic G-protein coupled receptors. PLoS Computational Biology. 2010;6(8):e1000884. DOI: 10.1371/journal.pcbi.1000884ca
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pcbi.1000884
• dc.identifier.issn 1553-734Xca
• dc.identifier.uri http://hdl.handle.net/10230/23430
• dc.language.iso engca
• dc.publisher Public Library of Science (PLoS)ca
• dc.relation.ispartof PLoS Computational Biology. 2010;6(8):e1000884
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2009-13609
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/FIS2008-01040
• dc.rights © 2010 Selent et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted 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 Proteïnes
• dc.subject.other Genoma humàca
• dc.title Induced effects of sodium ions on dopaminergic G-protein coupled receptorsen
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca