Zn(2+) site engineering at the oligomeric interface of the dopamine transporter
Research output: Contribution to journal › Journal article › Research › peer-review
Increasing evidence suggests that Na(+)/Cl(-)-dependent neurotransmitter transporters exist as homo-oligomeric proteins. However, the functional implication of this oligomerization remains unclear. Here we demonstrate the engineering of a Zn(2+) binding site at the predicted dimeric interface of the dopamine transporter (DAT) corresponding to the external end of transmembrane segment 6. Upon binding to this site, which involves a histidine inserted in position 310 (V310H) and the endogenous Cys306 within the same DAT molecule, Zn(2+) potently inhibits [(3)H]dopamine uptake. These data provide indirect evidence that conformational changes critical for the translocation process may occur at the interface between two transporter molecules in the oligomeric structure.
Original language | English |
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Journal | FEBS Letters |
Volume | 524 |
Issue number | 1-3 |
Pages (from-to) | 87-91 |
Number of pages | 5 |
ISSN | 0014-5793 |
Publication status | Published - 31 Jul 2002 |
- Animals, Biopolymers, COS Cells, Dopamine, Dopamine Plasma Membrane Transport Proteins, Humans, Membrane Glycoproteins, Membrane Transport Proteins, Mutagenesis, Site-Directed, Nerve Tissue Proteins, Polymerase Chain Reaction, Protein Binding, Zinc
Research areas
ID: 47293339