Possible Existence of Quaternary Structure in the High-Affinity Serotonin Transport Complex
| Autor: | Sharon M. Chang, Diane M. Starnes, Albert S. Chang |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Serotonin
Protein Conformation Biophysics Serotonin transport Nerve Tissue Proteins Transfection Biochemistry Mice Structure-Activity Relationship Cocaine Tetramer Animals GABA transporter Serotonin Uptake Inhibitors Molecular Biology Serotonin transporter Serotonin Plasma Membrane Transport Proteins Membrane Glycoproteins biology Membrane Transport Proteins Biological Transport Cell Biology Ligand (biochemistry) Kinetics Mutagenesis COS Cells biology.protein Protein quaternary structure Heterologous expression Carrier Proteins Dimerization Gene Deletion Selective Serotonin Reuptake Inhibitors |
| Zdroj: | Biochemical and Biophysical Research Communications. 249:416-421 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.1998.9158 |
| Popis: | Deletion-mutants of the cloned mouse serotonin transporter (SERT) rendered dominant negative-mutant effects upon wild-type transporter activities in heterologous expression studies; such effects were transporter-selective and did not influence the activities of co-expressed neuronal GABA transporter. Heterologous expression of linear concatenates (up to four copies) of SERT further revealed discernable uptake activities for both transporter-dimer and -tetramer, but not for the trimer. Kinetic and pharmacological analyses revealed that the monomer, dimer, and tetramer manifested comparable transport K m and potencies for known serotonin uptake inhibitors; the tetramer was distinct from the others only in manifesting notably reduced transport V max . Surprisingly, equivalent cocaine congener-binding activities were observed for all concatenates, including the functionally inactive trimer. These findings collectively support the existence of quaternary structure in the active 5-HT transport complex; such structure is likely to be a critical determinant of ligand transport activities, but apparently not of transporter–inhibitor interactions. |
| Databáze: | OpenAIRE |
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