TY - JOUR
T1 - Only one of the charged amino acids located in the transmembrane α-helices of the γ-aminobutyric acid transporter (subtype A) is essential for its activity
AU - Pantanowitz, Shifrah
AU - Bendahan, Annie
AU - Kanner, Baruch I.
PY - 1993/2/15
Y1 - 1993/2/15
N2 - The γ-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 α-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.
AB - The γ-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 α-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.
UR - http://www.scopus.com/inward/record.url?scp=0027532379&partnerID=8YFLogxK
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C2 - 8428999
AN - SCOPUS:0027532379
SN - 0021-9258
VL - 268
SP - 3222
EP - 3225
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -