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J. Biol. Chem., Vol. 268, Issue 5, 3222-3225, 02, 1993
S Pantanowitz, A Bendahan and BI Kanner
The gamma-aminobutyric acid (GABA) transporter (subtype A) is located in
nerve terminals and catalyses coupled electrogenic uptake of the
neurotransmitter with two or three sodium and one chloride ions. It
contains 599 amino acids and 12 putative membrane spanning alpha- helices
and is the first described member of a neurotransmitter transporter
superfamily. The membrane domain contains 5 charged amino acids which are
basically conserved. Using site-directed mutagenesis, we show that only one
of them, arginine 69, is absolutely essential for activity. It is located
in a highly conserved region encompassing parts of helices 1 and 2. The
three other positively charged amino acids and the only negative charged
one, glutamate 467, are not critical. These results suggest that the
translocation pathway of the sodium ions through the membrane does not
involve charged amino acid residues and underline the importance of the
highly conserved stretch between amino acids 66 and 86.
Only one of the charged amino acids located in the transmembrane alpha- helices of the gamma-aminobutyric acid transporter (subtype A) is essential for its activity
Department of Biochemistry, Hadassah Medical School, Hebrew University, Jerusalem, Israel.
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