The dopamine D receptor, belonging to the class A G protein-coupled receptors (GPCRs), is an important drug target for several diseases, including schizophrenia and Parkinson's disease. The D receptor can be activated by the natural neurotransmitter dopamine or by synthetic ligands, which in both cases leads to the receptor coupling with a G protein. In addition to receptor modulation by orthosteric or allosteric ligands, it has been shown that lipids may affect the behaviour of membrane proteins. We constructed a model of a D receptor with a long intracellular loop (ICL3) coupled with G or G proteins, embedded in a complex asymmetric membrane, and simulated it in complex with positive, negative or neutral allosteric ligands. In this study, we focused on the influence of ligand binding and G protein coupling on the membrane-receptor interactions. We show that there is a noticeable interplay between the cell membrane, G proteins, D receptor and its modulators.
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| http://dx.doi.org/10.3390/molecules27041335 | DOI Listing |
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