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

Atsuko Yamashita, Satinder K. Singh, Toshimitsu Kawate, Yan Jin and Eric Gouaux ()
Additional contact information
Atsuko Yamashita: Department of Biochemistry and Molecular Biophysics
Satinder K. Singh: Department of Biochemistry and Molecular Biophysics
Toshimitsu Kawate: Department of Biochemistry and Molecular Biophysics
Yan Jin: Columbia University
Eric Gouaux: Department of Biochemistry and Molecular Biophysics

Nature, 2005, vol. 437, issue 7056, 215-223

Abstract: 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.

Date: 2005
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/nature03978 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:437:y:2005:i:7056:d:10.1038_nature03978

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature03978

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().