Physico-chemical similarity of neurotransmitter receptor and transporter transmembrane domains.

ABSTRACT

Receptor and transporter of neurotransmitters similarity in ability of ligand-binding makes us consider them to possess the sites of similar structure and physico-chemical characteristics. However direct analysis of amino acid sequences alignment did not allow revealing such sites. For functionally similar proteins that differ in primary structure, the similarity extent is satisfactory estimated as based on physico-chemical properties of individual domain. We have analyzed transmembrane domains of a set of receptors and transporters of choline, norepinephrine, dopamine and serotonin. In our analysis in direction from extracellular border to intracellular one, amino acid sequences of transmembrane domains were divided into fragments each consisting of 4 amino acids. Every fragment was characterized by physico-chemical properties, such as hydrophilicity, hydrophobicity, polarity, etc. Hierarchical cluster analysis in space of the physico-chemical properties of these fragments was performed. As a result we have obtained both heterogeneous clusters, which contained receptor and transporter fragments, and homogeneous clusters which contained only receptor or transporter domains. An analysis of heterogeneous clusters has shown that the 4th, 5th and 6th transmembrane receptor domains and the 2d, 3d and 7th transmembrane transporter helices possess maximum similarity. The results obtained allow one to make a conclusion that these domains take part in formation of the ligand-binding centers.