Dataset Information

Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer.

ABSTRACT: The beta(2)-adrenoceptor (beta(2)AR) was one of the first Family A G protein-coupled receptors (GPCRs) shown to form oligomers in cellular membranes, yet we still know little about the number and arrangement of protomers in oligomers, the influence of ligands on the organization or stability of oligomers, or the requirement for other proteins to promote oligomerization. We used fluorescence resonance energy transfer (FRET) to characterize the oligomerization of purified beta(2)AR site-specifically labelled at three different positions with fluorophores and reconstituted into a model lipid bilayer. Our results suggest that the beta(2)AR is predominantly tetrameric following reconstitution into phospholipid vesicles. Agonists and antagonists have little effect on the relative orientation of protomers in oligomeric complexes. In contrast, binding of inverse agonists leads to significant increases in FRET efficiencies for most labelling pairs, suggesting that this class of ligand promotes tighter packing of protomers and/or the formation of more complex oligomers by reducing conformational fluctuations in individual protomers. The results provide new structural insights into beta(2)AR oligomerization and suggest a possible mechanism for the functional effects of inverse agonists.

SUBMITTER: Fung JJ

PROVIDER: S-EPMC2748299 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer.

Fung Juan José JJ Deupi Xavier X Pardo Leonardo L Yao Xiao Jie XJ Velez-Ruiz Gisselle A GA Devree Brian T BT Sunahara Roger K RK Kobilka Brian K BK

The EMBO journal 20090917 21

The beta(2)-adrenoceptor (beta(2)AR) was one of the first Family A G protein-coupled receptors (GPCRs) shown to form oligomers in cellular membranes, yet we still know little about the number and arrangement of protomers in oligomers, the influence of ligands on the organization or stability of oligomers, or the requirement for other proteins to promote oligomerization. We used fluorescence resonance energy transfer (FRET) to characterize the oligomerization of purified beta(2)AR site-specifical ...[more]

PMID: 19763081

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Dataset Information

Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer.

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Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer.

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