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.
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.
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DOI：
10.1016/s0021-9258(18)53681-4
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发表时间：
1993-02
期刊：
影响因子：
--
通讯作者：
S. Pantanowitz;A. Bendahan;B. Kanner
中科院分区：
文献类型：
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作者：
S. Pantanowitz;A. Bendahan;B. Kanner
γ-氨基丁酸（GABA）转运蛋白（A亚型）位于神经末梢，催化神经递质与两个或三个钠离子和一个氯离子的偶联生电摄取。它含有599个氨基酸和12个假定的跨膜α-螺旋，是神经递质转运蛋白超家族的第一个描述的成员。膜结构域含有5个基本保守的带电氨基酸。使用定点突变，我们表明，只有其中之一，精氨酸69，是绝对必要的活动。它位于高度保守的区域，包括螺旋1和2的部分。另外三种带正电荷的氨基酸和唯一带负电荷的氨基酸谷氨酸467并不重要。这些结果表明，钠离子通过膜的转运途径不涉及带电的氨基酸残基，并强调了氨基酸66和86之间的高度保守的拉伸的重要性。
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.