【摘 要】
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Excitatory amino acid transporter 1 (EAAT1) is a glutamate transporter which maintains low synaptic concentrations of the excitatory neurotransmitter, so that the extracellular glutamate concentration
【机 构】
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Department of Immunology, Southern Medical University, Guangzhou 510515, Guangdong,China
【出 处】
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Iternational Frontiers Symposium foe Neuron & Disease(国际神经与疾
论文部分内容阅读
Excitatory amino acid transporter 1 (EAAT1) is a glutamate transporter which maintains low synaptic concentrations of the excitatory neurotransmitter, so that the extracellular glutamate concentration is below neurotoxic level.The reentrant helical hairpin (HP) 1 locates toward the intracellular side and serves as part of the intracellular gate of the transporter.Opening of this intracellular gate, the transporter dissociates of sodium and substrate to the cytoplasm.However the mutual movement relationship between HP1 and transmembrane domain (TM) 2 during the transport cycle is not clear yet.We used paired cysteine mutagenesis to verify the predicted proximity of residues located at HP1 and TM2 of EAAT 1.A strong inhibition of transport by Copper(Ⅱ) (1,10-Phenanthroline)3 is observed in the double mutant V96C/S366C, but not in the corresponding single mutants.Transport by the mutant V96C/S366C also was inhibited by Cd2+.The inhibition was reduced in the presence of L-glu, or KCl, which favor the inward-facing conformation.This suggests that the cysteine residues are far apart in the inward-facing conformation.TBOA increases the proportion of protein trapped in an outward-facing conformation.TBOA caused a clear potentiation of this inhibition.This suggests that the cysteine residues are indeed closer together in the outward-facing conformation.Our results suggest that substrate and analogues can cause a relative movement between HP1 and TM2 of the glutamate transporter EAAT1 during the substrate transport, and the spatial relationship between HP1 and TM2 is changing during the transport cycle.
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