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@ARTICLE{Navarro:130228,
author = {G. Navarro and A. Cordomí and M. Zelman-Femiak$^*$ and M.
Brugarolas and E. Moreno and D. Aguinaga and L. Perez-Benito
and A. Cortés and V. Casadó and J. Mallol and E. I. Canela
and C. Lluís and L. Pardo and A. J. García-Sáez$^*$ and
P. J. McCormick and R. Franco},
title = {{Q}uaternary structure of a {G}-protein-coupled receptor
heterotetramer in complex with {G}i and {G}s.},
journal = {BMC biology},
volume = {14},
number = {1},
issn = {1741-7007},
address = {Berlin},
publisher = {Springer},
reportid = {DKFZ-2017-05308},
pages = {26},
year = {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 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.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.},
keywords = {Receptors, Purinergic P1 (NLM Chemicals) / Heterotrimeric
GTP-Binding Proteins (NLM Chemicals)},
cin = {B160},
ddc = {570},
cid = {I:(DE-He78)B160-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27048449},
pmc = {pmc:PMC4822319},
doi = {10.1186/s12915-016-0247-4},
url = {https://inrepo02.dkfz.de/record/130228},
}