A Usual G-Protein-Coupled Receptor in Unusual Membranes.
Angew Chem Int Ed Engl
; 55(2): 588-92, 2016 Jan 11.
Article
em En
| MEDLINE
| ID: mdl-26633591
ABSTRACT
G-protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and constitute about 50% of all known drug targets. They offer great potential for membrane protein nanotechnologies. We report here a charge-interaction-directed reconstitution mechanism that induces spontaneous insertion of bovine rhodopsin, the eukaryotic GPCR, into both lipid- and polymer-based artificial membranes. We reveal a new allosteric mode of rhodopsin activation incurred by the non-biological membranes the cationic membrane drives a transition from the inactive MI to the activated MII state in the absence of high [H(+)] or negative spontaneous curvature. We attribute this activation to the attractive charge interaction between the membrane surface and the deprotonated Glu134 residue of the rhodopsin-conserved ERY sequence motif that helps break the cytoplasmic "ionic lock". This study unveils a novel design concept of non-biological membranes to reconstitute and harness GPCR functions in synthetic systems.
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Base de dados:
MEDLINE
Assunto principal:
Receptores Acoplados a Proteínas G
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article