title: Neurotransmitter transporters: structure meets function.
abstract: At synapses, sodium-coupled transporters remove released neurotransmitters, thereby recycling them and maintaining a low extracellular concentration of the neurotransmitter. The molecular mechanism underlying sodium-coupled neurotransmitter uptake is not completely understood. Several structures of homologs of human neurotransmitter transporters have been solved with X-ray crystallography. These crystal structures have spurred a plethora of computational and experimental work to elucidate the molecular mechanism underlying sodium-coupled transport. Here, we compare the structures of GltPh, a glutamate transporter homolog, and LeuT, a homolog of neurotransmitter transporters for the biogenic amines and inhibitory molecules GABA and glycine. We relate these structures to data obtained from experiments and computational simulations, to draw conclusions about the mechanism of uptake by sodium-coupled neurotransmitter transporters. Here, we propose how sodium and substrate binding is coupled and how binding of sodium and substrate opens and closes the gates in these transporters, thereby leading to an efficient coupled transport.
authors.affiliation: Program in Chemical Biology, Department of Physiology and Pharmacology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Focke
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.forename: H Peter
authors.initials: HP
authors.lastname: Larsson
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D050479:Neurotransmitter Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D012964:Sodium / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D050479:Neurotransmitter Transport Proteins; D012964:Sodium