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| Home > Articles > Published articles > Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with G and G |
(Universitat de Barcelona. Departament de Bioquímica i Biomedicina Molecular) (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i Medicina Preventiva i Salut Pública) (Universitat de Barcelona. Departament de Bioquímica i Biomedicina Molecular) (Universitat de Barcelona. Departament de Bioquímica i Biomedicina Molecular) (Universitat de Barcelona. Departament de Bioquímica i Biomedicina Molecular) (Universitat de Barcelona. Departament de Bioquímica i Biomedicina Molecular) (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i Medicina Preventiva i Salut Pública) (Universitat de Barcelona. Departament de Bioquímica i Biomedicina Molecular)
| Date: | 2016 |
| Abstract: | 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. We used single-particle tracking experiments in cells expressing functional adenosine A-A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A receptor in the presence of the A 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. 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 (G and G). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function. The online version of this article (doi:10. 1186/s12915-016-0247-4) contains supplementary material, which is available to authorized users. |
| Grants: | Ministerio de Ciencia y Tecnología SAF2010/16089 Ministerio de Ciencia y Tecnología SAF2010-18472 Ministerio de Ciencia y Tecnología SAF2011-23813 Ministerio de Ciencia y Tecnología SAF2013-48271-C2-2-R |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | GPCR ; Heterotetramer ; Heterotrimeric G protein ; Single-particle tracking ; BRET ; Molecular modeling |
| Published in: | BMC biology, Vol. 14 (april 2016) , ISSN 1741-7007 |
