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Title: Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with Gi and Gs
Author: Navarro Brugal, Gemma
Cordomí, Arnau
Zelman-Femiak, Monika
Brugarolas Campillos, Marc
Moreno Guillén, Estefanía
Aguinaga Andrés, David
Pérez-Benito, Laura
Cortés Tejedor, Antonio
Casadó, Vicent
Mallol Montero, Josefa
Canela Campos, Enric I.
Lluís i Biset, Carme
Pardo, Leonardo
García-Saez, Ana J.
McCormick, Peter J.
Franco Fernández, Rafael
Keywords: Proteïnes
Models moleculars
Receptors cel·lulars
Molecular models
Cell receptors
Issue Date: 5-Apr-2016
Publisher: BioMed Central
Abstract: Background G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. Results We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. Conclusions The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function.
Note: Reproducció del document publicat a:
It is part of: Bmc Biology, 2016, vol. 14, num. 26, p. 1-10
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ISSN: 1741-7007
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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