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This research aims to understand how selective inhibitors affect the structure and function of the GABA transporter GAT3.

February 2, 2026Nature CommunicationsOpen Access

Structural basis for selective inhibition of human GABA transporter GAT3

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Cryo-electron microscopy reveals how GAT3 inhibitor binds, suggesting strategies for treating neurological disorders.

This research aims to understand how selective inhibitors affect the structure and function of the GABA transporter GAT3.
Utilized cryo-electron microscopy to visualize full-length human GAT3 structures.
Analyzed GAT3 in three states: bound to a selective inhibitor, bound to GABA, and in a substrate-free state.
Identified molecular interactions involved in GABA binding and transport inhibition.
GAT3 exhibits an inward-open conformation when bound to the inhibitor or substrate-free.
GABA-bound GAT3 shows an inward-occluded state, revealing critical ion coordination.
Inhibition selectivity is determined by specific molecular interactions within the transporter.

Mortensen et al. (2026) studied this question.

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