Two amino acid differences in the sixth transmembrane domain are partially responsible for the pharmacological differences between the 5-HT1D beta and 5-HT1E 5-hydroxytryptamine receptors
| Autor: | Eric M. Parker, Robert A. Shapiro, Lore Lewis-Higgins, Darcy G. Izzarelli, Dawn Palmer |
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| Rok vydání: | 1996 |
| Předmět: |
Serotonin
Recombinant Fusion Proteins Molecular Sequence Data Glutamic Acid Class C GPCR Biology Ligands Transfection Biochemistry Binding Competitive Polymerase Chain Reaction Rhodopsin-like receptors Protein Structure Secondary Cellular and Molecular Neuroscience Chlorocebus aethiops Serine Animals Humans Point Mutation Amino Acid Sequence Binding site Cloning Molecular Ergolines Isoleucine Receptor Peptide sequence G protein-coupled receptor DNA Primers Binding Sites Base Sequence Sequence Homology Amino Acid Lysine Models Structural Transmembrane domain Kinetics Receptors Serotonin COS Cells Receptor Serotonin 5-HT1B 5-HT1 receptor |
| Zdroj: | Journal of neurochemistry. 67(5) |
| ISSN: | 0022-3042 |
| Popis: | 5-Hydroxytryptamine elicits its physiological effects by interacting with a diverse group of receptors. Two of these receptors, the 5-HT1D beta and the 5-HT1E receptors, are approximately 60% identical in the transmembrane domains that presumably form the ligand binding site yet have very different pharmacological properties. Analysis of the pharmacological properties of a series of chimeric 5-HT1D beta/5-HT1E receptors indicates that sequences in the sixth and seventh transmembrane domains are responsible for the differential affinity of 5-carboxamidotryptamine for these two receptors. More detailed analysis shows that two amino acid differences in the sixth transmembrane domain (Ile333 and Ser334 in the 5-HT1D beta receptor, corresponding to Lys310 and Glu311 in the 5-HT1E receptor) are largely responsible for the differential affinities of some, but not all, ligands for the 5-HT1D beta and 5-HT1E receptors. It is likely that these two amino acids subtly determine the overall three-dimensional structure of the receptor rather than interact directly with individual ligands. |
| Databáze: | OpenAIRE |
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