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A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein.

ABSTRACT: G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the GPCR rhodopsin and several G proteins have been determined by x-ray crystallography, yet the organization of the signaling complex between GPCRs and G proteins is poorly understood. The observations that some GPCRs are obligate heterodimers, and that many GPCRs form both homo- and heterodimers, has led to speculation that GPCR dimers may be required for efficient activation of G proteins. However, technical limitations have precluded a definitive analysis of G protein coupling to monomeric GPCRs in a biochemically defined and membrane-bound system. Here we demonstrate that a prototypical GPCR, the beta2-adrenergic receptor (beta2AR), can be incorporated into a reconstituted high-density lipoprotein (rHDL) phospholipid bilayer particle together with the stimulatory heterotrimeric G protein, Gs. Single-molecule fluorescence imaging and FRET analysis demonstrate that a single beta2AR is incorporated per rHDL particle. The monomeric beta2AR efficiently activates Gs and displays GTP-sensitive allosteric ligand-binding properties. These data suggest that a monomeric receptor in a lipid bilayer is the minimal functional unit necessary for signaling, and that the cooperativity of agonist binding is due to G protein association with a receptor monomer and not receptor oligomerization.

SUBMITTER: Whorton MR

PROVIDER: S-EPMC1863461 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein.

Whorton Matthew R MR Bokoch Michael P MP Rasmussen Søren G F SG Huang Bo B Zare Richard N RN Kobilka Brian B Sunahara Roger K RK

Proceedings of the National Academy of Sciences of the United States of America 20070423 18

G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the GPCR rhodopsin and several G proteins have been determined by x-ray crystallography, yet the organization of the signaling complex between GPCRs and G proteins is poorly understood. The observations that some GPCRs are obligate heterodimers, and that many GPCRs form both homo- and heterodimers, h ...[more]

PMID: 17452637

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Dataset Information

A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein.

Publications

A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein.

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