Re: Neurotransmitter receptor binding mechanisms

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




References:


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