
GAT1 수송체는 나트륨 이온 결합을 통해 기질 GABA의 결합을 안정화하고, 수송체의 구조를 조절하여 효율적인 GABA 재흡수를 가능하게 한다.


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The human GABA transporter (GAT1) is a membrane transporter that mediates the reuptake of the neurotransmitter GABA from the synaptic cleft into neurons and glial cells. Dysregulation of the transport cycle has been associated with epilepsy and neuropsychiatric disorders, highlighting the crucial role of the transporter in maintaining homeostasis of brain GABA levels. GAT1 is a secondary active transporter that couples the movement of substrate to the simultaneous transport of sodium and chloride ions along their electrochemical gradients. Using MD simulations, we identified a novel sodium recruiting site at the entrance to the outer vestibule, which attracts positively charged ions and increases the local sodium concentration, thereby indirectly increasing sodium affinity. Mutations of negatively charged residues at the recruiting site slowed the binding kinetics, while experimental data revealed a change in sodium dependency of GABA uptake and a reduction of sodium affinity. Simulation showed that sodium displays a higher affinity for the sodium binding site NA2, which plays a role in stabilisation of the outward-open conformation. We directly show that the presence of a sodium ion bound to NA2 increases the stability of the closed inner gate and restrains motions of TM5. We find that sodium is only weakly bound to NA1 in the absence of GABA, while the presence of the substrate strengthens the interaction due to the completed ion coordinating shell, explaining cooperativity between GABA and sodium.

### Competing Interest Statement

The authors have declared no competing interest.

Interaction of GAT1 with sodium ions: from efficient recruitment to stabilisation of substrate and conformation

gat1-수송체의-나트륨-이온과의-상호작용-효율적인-유치에서-기질-및-구조-안정화까지


GAT1 수송체의 나트륨 이온과의 상호작용: 효율적인 유치에서 기질 및 구조 안정화까지
