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Zn 2+ site engineering at the oligomeric interface of the dopamine transporter
Author(s) -
Norgaard-Nielsen Kristine,
Norregaard Lene,
Hastrup Hanne,
Javitch Jonathan A,
Gether Ulrik
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03008-9
Subject(s) - dopamine transporter , dopamine plasma membrane transport proteins , neurotransmitter transporter , transporter , chemistry , dopamine , biophysics , transmembrane protein , binding site , histidine , biochemistry , biology , amino acid , neuroscience , receptor , gene
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.