Gene

Reuptake inhibitor

Monoaminergic

Neurotransmitter

Cell biology

Neuroscience

Biology

Dynamics (music)

Monoamine neurotransmitter

Receptor

Agonist

Neurotransmitter transporter

Neurotransmission

Biochemistry

Acoustics

Protein structure

Dopamine

Antidepressant

Computational biology

Reuptake

Physics

Transporter

Intrinsic activity

Synaptic cleft

Hippocampus

Central nervous system

Allosteric regulation

Norepinephrine

Protein dynamics

Chemistry

Biophysics

Serotonin

Nature Structural & Molecular Biology

Monoamine transporters (MATs) regulate neurotransmission via the reuptake of dopamine, serotonin and norepinephrine from extra-neuronal regions and thus maintain neurotransmitter homeostasis. As targets of a wide range of compounds, including antidepressants, substances of abuse and drugs for neuropsychiatric and neurodegenerative disorders, their mechanism of action and their modulation by small molecules have long been of broad interest. Recent advances in the structural characterization of dopamine and serotonin transporters have opened the way for structure-based modeling and simulations, which, together with experimental data, now provide mechanistic understanding of their transport function and interactions. Here we review recent progress in the elucidation of the structural dynamics of MATs and their conformational landscape and transitions, as well as allosteric regulation mechanisms. Monoamine transporters (MATs) regulate neurotransmission via the reuptake of dopamine, serotonin and norepinephrine from the extra-neuronal space. This Review discusses recent advances in elucidating the structural dynamics and allosteric regulation of MATs.

Monoamine transporters: structure, intrinsic dynamics and allosteric regulation