6X15

Inward-facing state of the glutamate transporter homologue GltPh in complex with L-aspartate and sodium ions

Summary for 6X15

• Entry DOI: 10.2210/pdb6x15/pdb
• EMDB information: 21986 21987 21988 21989 21990 21991
• Descriptor: Glutamate transporter homologue GltPh, SODIUM ION, ASPARTIC ACID, ... (6 entities in total)
• Functional Keywords: sodium-coupled l-aspartate transporter, transport protein
• Biological source: Pyrococcus horikoshii
• Total number of polymer chains: 3
• Total formula weight: 163141.59

Authors

Wang, X.,Boudker, O. (deposition date: 2020-05-18, release date: 2020-11-18, Last modification date: 2024-11-13)

Primary citation

Wang, X.,Boudker, O.
Large domain movements through the lipid bilayer mediate substrate release and inhibition of glutamate transporters.
Elife, 9:-, 2020

PubMed Abstract: Glutamate transporters are essential players in glutamatergic neurotransmission in the brain, where they maintain extracellular glutamate below cytotoxic levels and allow for rounds of transmission. The structural bases of their function are well established, particularly within a model archaeal homolog, sodium, and aspartate symporter Glt. However, the mechanism of gating on the cytoplasmic side of the membrane remains ambiguous. We report Cryo-EM structures of Glt reconstituted into nanodiscs, including those structurally constrained in the cytoplasm-facing state and either apo, bound to sodium ions only, substrate, or blockers. The structures show that both substrate translocation and release involve movements of the bulky transport domain through the lipid bilayer. They further reveal a novel mode of inhibitor binding and show how solutes release is coupled to protein conformational changes. Finally, we describe how domain movements are associated with the displacement of bound lipids and significant membrane deformations, highlighting the potential regulatory role of the bilayer.

PubMed: 33155546
DOI: 10.7554/eLife.58417

Experimental method

ELECTRON MICROSCOPY (3.05 Å)