title: How LeuT shapes our understanding of the mechanisms of sodium-coupled neurotransmitter transporters.
abstract: Neurotransmitter transporters are ion-coupled symporters that drive the uptake of neurotransmitters from neural synapses. In the past decade, the structure of a bacterial amino acid transporter, leucine transporter (LeuT), has given valuable insights into the understanding of architecture and mechanism of mammalian neurotransmitter transporters. Different conformations of LeuT, including a substrate-free state, inward-open state, and competitive and non-competitive inhibitor-bound states, have revealed a mechanistic framework for the transport and transport inhibition of neurotransmitters. The current review integrates our understanding of the mechanistic and pharmacological properties of eukaryotic neurotransmitter transporters obtained through structural snapshots of LeuT.
authors.affiliation: Vollum Institute and Howard Hughes Medical Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. gouauxe@ohsu.edu.
authors.forename: Aravind
authors.initials: A
authors.lastname: Penmatsa
authors.forename: Eric
authors.initials: E
authors.lastname: Gouaux
mesh_terms: D026905:Amino Acid Transport Systems / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007930:Leucine / Q000378:metabolism*; D008956:Models, Chemical; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000378:metabolism*; D050479:Neurotransmitter Transport Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D011487:Protein Conformation; D012964:Sodium / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D026905:Amino Acid Transport Systems; D018377:Neurotransmitter Agents; D050479:Neurotransmitter Transport Proteins; D012964:Sodium; D007930:Leucine