Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with Gi and Gs

• DOI: 10.1186/s12915-016-0247-4
• Publication Date: 2016-04-05T11:18:47Z
• Authors: Gemma Navarro; Arnau Cordomí; Monika Zelman-Femiak; Marc Brugarolas; Estefania Moreno; David Aguinaga; Laura Perez-Benito; Antoni Cortés; Vicent Casadó; Josefa Mallol; Enric I. Canela; Carme Lluís; Leonardo Pardo; Ana J. García-Sáez; Peter J. McCormick; Rafael Franco
• Keywords: Heterotetramer; G beta-gamma complex; Protein quaternary structure

G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental transfer extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact heteromers novel units. Despite exponential growth number solved GPCR crystal structures, structural properties remain unknown. We used single-particle tracking experiments cells expressing functional adenosine A1-A2A fused fluorescent proteins show loss Brownian movement A1 receptor presence A2A receptor, and a preponderance cell surface 2:2 (dimer dimers). Using computer modeling, aided by bioluminescence resonance energy assays monitor homomerization heteromerization G-protein coupling, we predict interacting interfaces propose quaternary structure tetramer complex with two proteins. The combination results points molecular architecture formed rhombus-shaped heterotetramer, which is bound different (Gi Gs). These constitute an important advance understanding intricacies involved function.