Coupled ion binding and structural transitions along the transport cycle of glutamate transporters

Abstract
Article and author information
Metrics

Abstract

Membrane transporters that clear the neurotransmitter glutamate from synapses are driven by symport of sodium ions and counter-transport of a potassium ion. Previous crystal structures of a homologous archaeal sodium and aspartate symporter showed that a dedicated transport domain carries the substrate and ions across the membrane. Here, we report new crystal structures of this homologue in ligand-free and ions-only bound outward- and inward-facing conformations. We show that after ligand release, the apo transport domain adopts a compact and occluded conformation that can traverse the membrane, completing the transport cycle. Sodium binding primes the transport domain to accept its substrate and triggers extracellular gate opening, which prevents inward domain translocation until substrate binding takes place. Furthermore, we describe a new cation-binding site ideally suited to bind a counter-transported ion. We suggest that potassium binding at this site stabilizes the translocation-competent conformation of the unloaded transport domain in mammalian homologues.

Article and author information

Author details

Grégory Verdon

Imperial College London, South Kensington, United Kingdom

Competing interests
The authors declare that no competing interests exist.
SeCheol Oh

Weill Cornell Medical College, New York, United States

Competing interests
The authors declare that no competing interests exist.
Ryan N Serio

Weill Cornell Medical College, New York, United States

Competing interests
The authors declare that no competing interests exist.
Olga Boudker

Weill Cornell Medical College, New York, United States

For correspondence
olb2003@med.cornell.edu

Competing interests
The authors declare that no competing interests exist.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.