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キーワード
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

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Structure paper

タイトル	Glutamate transporters have a chloride channel with two hydrophobic gates.
ジャーナル・号・ページ	Nature, Vol. 591, Issue 7849, Page 327-331, Year 2021
掲載日	2021年2月17日
著者	Ichia Chen / Shashank Pant / Qianyi Wu / Rosemary J Cater / Meghna Sobti / Robert J Vandenberg / Alastair G Stewart / Emad Tajkhorshid / Josep Font / Renae M Ryan /
PubMed 要旨	Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and its precise control is vital to maintain normal brain function and to prevent excitotoxicity. The removal ...Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and its precise control is vital to maintain normal brain function and to prevent excitotoxicity. The removal of extracellular glutamate is achieved by plasma-membrane-bound transporters, which couple glutamate transport to sodium, potassium and pH gradients using an elevator mechanism. Glutamate transporters also conduct chloride ions by means of a channel-like process that is thermodynamically uncoupled from transport. However, the molecular mechanisms that enable these dual-function transporters to carry out two seemingly contradictory roles are unknown. Here we report the cryo-electron microscopy structure of a glutamate transporter homologue in an open-channel state, which reveals an aqueous cavity that is formed during the glutamate transport cycle. The functional properties of this cavity, combined with molecular dynamics simulations, reveal it to be an aqueous-accessible chloride permeation pathway that is gated by two hydrophobic regions and is conserved across mammalian and archaeal glutamate transporters. Our findings provide insight into the mechanism by which glutamate transporters support their dual function, and add information that will assist in mapping the complete transport cycle shared by the solute carrier 1A transporter family.
リンク	Nature / PubMed:33597752 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	3.45 - 4.0 Å
構造データ	21966 6wyj EMDB-21966: Cryo-EM structure of the GltPh L152C-G321C mutant in the intermediate state. PDB-6wyj: Cryo-EM structure of the GltPh L152C-G321C mutant in the intermediate state 手法: EM (単粒子) / 解像度: 3.7 Å 21967 6wyk EMDB-21967, PDB-6wyk: Cryo-EM structure of the GltPh L152C-G321C mutant in the intermediate chloride conducting state. 手法: EM (単粒子) / 解像度: 4.0 Å 21968 6wyl EMDB-21968, PDB-6wyl: Cryo-EM structure of GltPh L152C-G351C mutant in the intermediate outward-facing state. 手法: EM (単粒子) / 解像度: 3.9 Å PDB-6wzb: Crystal structure of the GltPh V216C-G388C mutant cross-linked with divalent mercury 手法: X-RAY DIFFRACTION / 解像度: 3.45 Å PDB-6x01: Crystal structure of the GltPh V216C-A391C mutant cross-linked in outward-facing state 手法: X-RAY DIFFRACTION / 解像度: 3.65 Å
化合物	ChemComp-ASP: ASPARTIC ACID / アスパラギン酸 ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-HG: Unknown entry
由来	Pyrococcus horikoshii OT3 (古細菌) pyrococcus horikoshii (strain atcc 700860 / dsm 12428 / jcm 9974 / nbrc 100139 / ot-3) (古細菌)
キーワード	TRANSPORT PROTEIN / Glutamate transporter homolog Gltph / Glutamate transporter homolog