EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	The ion-coupling mechanism of human excitatory amino acid transporters.
ジャーナル・号・ページ	EMBO J, Vol. 41, Issue 1, Page e108341, Year 2022
掲載日	2022年1月4日
著者	Juan C Canul-Tec / Anand Kumar / Jonathan Dhenin / Reda Assal / Pierre Legrand / Martial Rey / Julia Chamot-Rooke / Nicolas Reyes /
PubMed 要旨	Excitatory amino acid transporters (EAATs) maintain glutamate gradients in the brain essential for neurotransmission and to prevent neuronal death. They use ionic gradients as energy source and co- ...Excitatory amino acid transporters (EAATs) maintain glutamate gradients in the brain essential for neurotransmission and to prevent neuronal death. They use ionic gradients as energy source and co-transport transmitter into the cytoplasm with Na and H , while counter-transporting K to re-initiate the transport cycle. However, the molecular mechanisms underlying ion-coupled transport remain incompletely understood. Here, we present 3D X-ray crystallographic and cryo-EM structures, as well as thermodynamic analysis of human EAAT1 in different ion bound conformations, including elusive counter-transport ion bound states. Binding energies of Na and H , and unexpectedly Ca , are coupled to neurotransmitter binding. Ca competes for a conserved Na site, suggesting a regulatory role for Ca in glutamate transport at the synapse, while H binds to a conserved glutamate residue stabilizing substrate occlusion. The counter-transported ion binding site overlaps with that of glutamate, revealing the K -based mechanism to exclude the transmitter during the transport cycle and to prevent its neurotoxic release on the extracellular side.
リンク	EMBO J / PubMed:34747040 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	3.25 - 3.99 Å
構造データ	12524 7npw EMDB-12524, PDB-7npw: Cryo-EM structure of Human excitatory amino acid transporters-1 (EAAT1) in potassium buffer 手法: EM (単粒子) / 解像度: 3.99 Å PDB-7awl: Structure of the thermostabilized EAAT1 cryst-II mutant in complex with barium and the allosteric inhibitor UCPH101 手法: X-RAY DIFFRACTION / 解像度: 3.7 Å PDB-7awm: Structure of the thermostabilized EAAT1 cryst mutant in complex with L-ASP, three sodium ions and the allosteric inhibitor UCPH101 手法: X-RAY DIFFRACTION / 解像度: 3.25 Å PDB-7awn: Structure of the thermostabilized EAAT1 cryst mutant in complex with rubidium and barium and the allosteric inhibitor UCPH101 手法: X-RAY DIFFRACTION / 解像度: 3.92 Å PDB-7awp: Structure of the thermostabilized EAAT1 cryst-II mutant in complex with rubidium and barium ions and the allosteric inhibitor UCPH101 手法: X-RAY DIFFRACTION / 解像度: 3.91 Å PDB-7awq: Structure of the thermostabilized EAAT1 cryst-E386Q mutant in complex with L-ASP, sodium ions and the allosteric inhibitor UCPH101 手法: X-RAY DIFFRACTION / 解像度: 3.65 Å
化合物	ChemComp-6Z6: 2-Amino-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-4H-chromene-3-carbonitrile ChemComp-BA: Unknown entry / バリウムジカチオン ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-ASP: ASPARTIC ACID / アスパラギン酸 ChemComp-RB: RUBIDIUM ION / ルビジウムカチオン
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / excitatory amino acid transporter 1 / human glutamate transporter / SLC1A3 / ion-coupling mechanism / allosteric inhibitor UCPH101 / TRANSPORT PROTEIN / Human Membrane Protein / Transporter / Glutamate transporter