6X14

Inward-facing state of the glutamate transporter homologue GltPh in complex with TFB-TBOA

6X14 の概要

• エントリーDOI: 10.2210/pdb6x14/pdb
• EMDBエントリー: 21986 21987 21988 21989 21990 21991
• 分子名称: Glutamate transporter homologue GltPh, (2~{S},3~{S})-2-azanyl-3-[[3-[[4-(trifluoromethyl)phenyl]carbonylamino]phenyl]methoxy]butanedioic acid, [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate (3 entities in total)
• 機能のキーワード: sodium-coupled l-aspartate transporter, transport protein
• 由来する生物種: Pyrococcus horikoshii
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 139518.76

構造登録者

Wang, X.,Boudker, O. (登録日: 2020-05-18, 公開日: 2020-11-18, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.71 Å)