RT Journal Article
T1 Characterization of the A2AR-D2R interface: Focus on the role of the C-terminal tail and the transmembrane helices
A1 Borroto-Escuela, Dasiel O.
A1 Romero-Fernandez, Wilber
A1 Tarakanov, Alexander O.
A1 Gómez-Soler, Maricel
A1 Corrales, Fidel
A1 Marcellino, Daniel
A1 Narvaez, Manuel
A1 Frankowska, Malgorzata
A1 Flajolet, Marc
A1 Heintz, Nathaniel
A1 Agnati, Luigi F.
A1 Ciruela, Francisco
A1 Fuxe, Kjell
K1 Dopamina - Receptores
AB A single serine point mutation (S374A) in the adenosine A2A receptor (A2AR) C-terminal tail reduces A2AR-D2R heteromerization and prevents its allosteric modulation of the dopamine D2 receptor (D2R). By means of site directed mutagenesis of the A2AR and synthetic transmembrane (TM) α-helix peptides of the D2R we further explored the role of electrostatic interactions and TM helix interactions of the A2AR-D2R heteromer interface. We found evidence that the TM domains IV and V of the D2R play a major role in the A2AR-D2R heteromer interface since the incubation with peptides corresponding to these domains significantly reduced the ability of A2AR and D2R to heteromerize. In addition, the incubation with TM-IV or TM-V blocked the allosteric modulation normally found in A2AR-D2R heteromers. The mutation of two negatively charged aspartates in the A2AR C-terminal tail (D401A/D402A) in combination with the S374A mutation drastically reduced the physical A2AR-D2R interaction and lost the ability of antagonistic allosteric modulation over the A2AR-D2R interface, suggesting further evidence for the existence of an electrostatic interaction between the C-terminal tail of A2AR and the intracellular loop 3 (IL3) of D2R. On the other hand, molecular dynamic model and bioinformatic analysis propose that specific AAR, AQE, and VLS protriplets as an important motive in the A2AR-D2LR heteromer interface together with D2LR TM segments IV/V interacting with A2AR TM-IV/V or TM-I/VII.
PB Elsevier
SN 10902104
YR 2010
FD 2010-11-26
LK https://hdl.handle.net/10630/45004
UL https://hdl.handle.net/10630/45004
LA eng
NO Dasiel O. Borroto-Escuela, Wilber Romero-Fernandez, Alexander O. Tarakanov, Maricel Gómez-Soler, Fidel Corrales, Daniel Marcellino, Manuel Narvaez, Malgorzata Frankowska, Marc Flajolet, Nathaniel Heintz, Luigi F. Agnati, Francisco Ciruela, Kjell Fuxe, Characterization of the A2AR–D2R interface: Focus on the role of the C-terminal tail and the transmembrane helices, Biochemical and Biophysical Research Communications, Volume 402, Issue 4, 2010, Pages 801-807, ISSN 0006-291X, https://doi.org/10.1016/j.bbrc.2010.10.122. (https://www.sciencedirect.com/science/article/pii/S0006291X10020115)
NO Swedish Medical Research Council
NO Torsten and Ragnar Söderberg Foundation
NO Hjärnfonden
NO Marianne and Marcus Wallenberg Foundation
NO Ministerio de Ciencia e Innovación (España)
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 3 mar 2026