2026-05-29T23:32:58Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/450042026-01-30T00:47:33Zcom_10630_2254col_10630_37953

Characterization of the A2AR-D2R interface: Focus on the role of the C-terminal tail and the transmembrane helices Borroto-Escuela, Dasiel O. Romero-Fernandez, Wilber Tarakanov, Alexander O. Gómez-Soler, Maricel Corrales, Fidel Marcellino, Daniel Narvaez, Manuel Frankowska, Malgorzata Flajolet, Marc Heintz, Nathaniel Agnati, Luigi F. Ciruela, Francisco Fuxe, Kjell Dopamina - Receptores 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. 2010-11-26 journal article 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) 10902104 https://hdl.handle.net/10630/45004 10.1016/j.bbrc.2010.10.122 eng info:eu-repo/grantAgreement/Swedish_Research_Council//04X-715/SE/// info:eu-repo/grantAgreement/MICINN/SAF/SAF2008-01462/ES/// info:eu-repo/grantAgreement/MICINN/Consolider-Ingenio/CSD2008-00005/ES/// http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 International Elsevier