4P6H: Tl+-bound Inward-facing State (bound Conformation) Of The Glutamate Transporter Homologue Gltph

Citation:
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.DOI: http://dx.doi.org/10.7554/eLife.02283.001.
PDB ID: 4P6HDownload
MMDB ID: 120503
PDB Deposition Date: 2014/3/24
Updated in MMDB: 2014/08
Experimental Method:
x-ray diffraction
Resolution: 4.08  Å
Source Organism:
Similar Structures:
Biological Unit for 4P6H: trimeric; determined by author and by software (PISA)
Molecular Components in 4P6H
Label Count Molecule
Proteins (3 molecules)
3
Gltph
Molecule annotation
Chemicals (9 molecules)
1
3
2
6
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.