|MadSci Network: Neuroscience|
The short answer to your question is yes, there has been extensive work done on identifying the binding sites of serotonin (5-hydroxytryptamine) to its receptors and of dopamine to its receptors. As you state, this adds to the ability of scientists to study receptor biology. I will give a little bit of background to your question. Both serotonin and dopamine are neurotransmitters which bind to G protein-coupled receptors (GPCRs). This class of receptors have 7 transmembrane segments (TMS) and are coupled to guanine nucleotide binding proteins (G proteins) as part of their signaling pathway. Through mutational studies in which amino acids in the protein are replaced by other amino acid residues, those residues which are crucial for the binding of ligand have been identified. For dopamine it appears there is a conserved aspartic acid residue located two helical turns from the extracellular surface of TMS3 as a critical docking site for the protonatable amine moiety of agonists and antagonists Like other amine neurotransmitters that activate GPCRs, 5- hydroxytryptamine (5-HT) binds to the 5-HT2A receptor through the interaction of its cationic primary amino group with the conserved Asp in transmembrane helix 3.
Figure: The attached figure shows a cartoon of the third TSM of a GPCR and the residues critical for binding ligand.
hope this helps,
gabriel vargas, md/ph
Nonconserved Residues in the Second Transmembrane-Spanning Domain of the D4 Dopamine Receptor Are Molecular Determinants of D4-Selective Pharmacology
John A. Schetz, Peter S. Benjamin, and David R. Sibley Molecular Pharmacology Vol. 57, Issue 1, 144-152, January 2000
Mapping the Binding Site Pocket of the Serotonin 5-Hydroxytryptamine2A Receptor Ser3.36(159) PROVIDES A SECOND INTERACTION SITE FOR THE PROTONATED AMINE OF SEROTONIN BUT NOT OF LYSERGIC ACID DIETHYLAMIDE OR BUFOTENIN*
Journal of Biological Chemistry Volume 271, Number 25, Issue of June 21, 1996 pp. 14672-14675
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