The role of conserved aspartate and serine residues in ligand binding and in function of the 5-HT 1A receptor: A site-directed mutation study

• Published in: FEBS letters Vol. 312; no. 2; pp. 259 - 262
• Main Authors: Ho, Begonia Y., Karschin, Andreas, Branchek, Theresa, Davidson, Norman, Lester, Henry A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 09.11.1992
• Subjects: COS-7 cell; GTPase; Receptor affinity; Serotonin 5-HT 1A receptor; Vaccinia virus vector; Receptor affinity; Serotonin 5-HT 1A receptor; GTPase; COS-7 cell; Vaccinia virus vector
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(92)80948-G

Wild-type and mutant serotonin 1A receptors were transiently expressed in COS-7 cells using the infection-transfection variant of the vaccinia virus/ T7 polymerase vector system. The amino acid substitutions in the transmembrane regions, Asp 82→Asn 82, Asp 116 →Asn 116, and Ser 198→Ala 198 all resulted in a decrease in affinity for 5-HT by 60–100-fold, without affecting the affinity for the antagonist, pindolol. The binding of agonist to the additional mutant, Thr 199→Ala 199, was too weak to be measured, 5-HT induced GTPase activities for all receptors studied. These findings indicate that the residues mutated play an important role in the binding of the agonist and less critical roles in the binding of the antagonist pindolol.