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Two Amino Acid Differences in the Sixth Transmembrane Domain Are Partially Responsible for the Pharmacological Differences Between the 5‐HT 1Dβ and 5‐HT 1E 5‐Hydroxytryptamine Receptors
Author(s) -
Parker Eric M.,
Izzarelli Darcy G.,
LewisHiggins Lore,
Palmer Dawn,
Shapiro Robert A.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67052096.x
Subject(s) - receptor , transmembrane domain , 5 ht receptor , transmembrane protein , affinities , amino acid , biology , serotonin , ligand (biochemistry) , biochemistry
5‐Hydroxytryptamine elicits its physiological effects by interacting with a diverse group of receptors. Two of these receptors, the 5‐HT 1Dβ and the 5‐HT 1E receptors, are ∼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‐HT 1Dβ /5‐HT 1E 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 (Ile 333 and Ser 334 in the 5‐HT 1Dβ receptor, corresponding to Lys 310 and Glu 311 in the 5‐HT 1E receptor) are largely responsible for the differential affinities of some, but not all, ligands for the 5‐HT 1Dβ and 5‐HT 1E 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.