Class A G protein-coupled receptors assemble into functional higher-order hetero-oligomers

FEBS Letters

article

Xianlong Gao¹  Garrett A. Enten¹  Anthony J. DeSantis¹  Matthias Majetschak¹ 

[1] Department of Surgery, Morsani College of Medicine, University of South Florida;Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida

关键词: ɑ1-adrenergic receptor;    ACKR3;    AVPR1A;    CXCR4;    receptor dimer;    receptor hetero-oligomerization;   

DOI  :  10.1002/1873-3468.14135

来源: John Wiley & Sons Ltd.

【 摘 要 】

Although class A seven-transmembrane helix (7TM) receptor hetero-oligomers have been proposed, information on the assembly and function of such higher-order hetero-oligomers is not available. Utilizing bioluminescence resonance energy transfer (BRET), bimolecular luminescence/fluorescence complementation (BiLC/BiFC), and BiLC/BiFC BRET in HEK293T cells, we provide evidence that chemokine (C-X-C motif) receptor 4, atypical chemokine receptor 3, α 1a -adrenoceptor, and arginine vasopressin receptor 1A form hetero-oligomers composed of 2–4 different protomers. We show that hetero-oligomerization per se and ligand binding to individual protomers regulate agonist-induced coupling to the signaling transducers of interacting receptor partners. Our findings support the concept that receptor hetero-oligomers form supramolecular machineries with molecular signaling properties distinct from the individual protomers. These findings provide a mechanism for the phenomenon of context-dependent receptor function.

【 授权许可】

Unknown