Crystal structure of a bacterial homologue of Na+/Cl --dependent neurotransmitter transporters

Atsuko Yamashita, Satinder K. Singh, Toshimitsu Kawate, Yan Jin, Eric Gouaux

Research output: Contribution to journalArticle

1179 Citations (Scopus)

Abstract

Na+/Cl--dependent transporters terminate synaptic transmission by using electrochemical gradients to drive the uptake of neurotransmitters, including the biogenic amines, from the synapse to the cytoplasm of neurons and glia. These transporters are the targets of therapeutic and illicit compounds, and their dysfunction has been implicated in multiple diseases of the nervous system. Here we present the crystal structure of a bacterial homologue of these transporters from Aquifex aeolicus, in complex with its substrate, leucine, and two sodium ions. The protein core consists of the first ten of twelve transmembrane segments, with segments 1-5 related to 6-10 by a pseudo-two-fold axis in the membrane plane. Leucine and the sodium ions are bound within the protein core, halfway across the membrane bilayer, in an occluded site devoid of water. The leucine and ion binding sites are defined by partially unwound transmembrane helices, with main-chain atoms and helix dipoles having key roles in substrate and ion binding. The structure reveals the architecture of this important class of transporter, illuminates the determinants of substrate binding and ion selectivity, and defines the external and internal gates.

Original languageEnglish
Pages (from-to)215-223
Number of pages9
JournalNature
Volume437
Issue number7056
DOIs
Publication statusPublished - Sep 8 2005
Externally publishedYes

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Neurotransmitter Transport Proteins
Bacterial Structures
Ions
Leucine
Sodium
Biogenic Amines
Membranes
Nervous System Diseases
Synaptic Transmission
Neuroglia
Synapses
Neurotransmitter Agents
Cytoplasm
Proteins
Binding Sites
Neurons
Water

ASJC Scopus subject areas

  • General

Cite this

Crystal structure of a bacterial homologue of Na+/Cl --dependent neurotransmitter transporters. / Yamashita, Atsuko; Singh, Satinder K.; Kawate, Toshimitsu; Jin, Yan; Gouaux, Eric.

In: Nature, Vol. 437, No. 7056, 08.09.2005, p. 215-223.

Research output: Contribution to journalArticle

Yamashita, Atsuko ; Singh, Satinder K. ; Kawate, Toshimitsu ; Jin, Yan ; Gouaux, Eric. / Crystal structure of a bacterial homologue of Na+/Cl --dependent neurotransmitter transporters. In: Nature. 2005 ; Vol. 437, No. 7056. pp. 215-223.
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