- PDB-6wu4: Structure of the LaINDY-alpha-ketoglutarate complex -
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基本情報
登録情報
データベース: PDB / ID: 6wu4
タイトル
Structure of the LaINDY-alpha-ketoglutarate complex
要素
DASS family sodium-coupled anion symporter
キーワード
MEMBRANE PROTEIN (膜タンパク質) / Transporter (運搬体タンパク質) / Structural Genomics (構造ゲノミクス) / PSI-Biology / New York Consortium on Membrane Protein Structure / NYCOMPS
機能・相同性
Citrate carrier CitT-related / Sodium:sulfate symporter transmembrane region / Solute carrier family 13 / transmembrane transporter activity / membrane => GO:0016020 / 生体膜 / DASS family sodium-coupled anion symporter / 2-oxoglutarate-malate translocator
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
U54GM095315
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01NS108151
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM121994
米国
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
R01DK099023
米国
引用
ジャーナル: Elife / 年: 2020 タイトル: Structural basis for the reaction cycle of DASS dicarboxylate transporters. 著者: David B Sauer / Noah Trebesch / Jennifer J Marden / Nicolette Cocco / Jinmei Song / Akiko Koide / Shohei Koide / Emad Tajkhorshid / Da-Neng Wang / 要旨: Citrate, α-ketoglutarate and succinate are TCA cycle intermediates that also play essential roles in metabolic signaling and cellular regulation. These di- and tricarboxylates are imported into the ...Citrate, α-ketoglutarate and succinate are TCA cycle intermediates that also play essential roles in metabolic signaling and cellular regulation. These di- and tricarboxylates are imported into the cell by the divalent anion sodium symporter (DASS) family of plasma membrane transporters, which contains both cotransporters and exchangers. While DASS proteins transport substrates via an elevator mechanism, to date structures are only available for a single DASS cotransporter protein in a substrate-bound, inward-facing state. We report multiple cryo-EM and X-ray structures in four different states, including three hitherto unseen states, along with molecular dynamics simulations, of both a cotransporter and an exchanger. Comparison of these outward- and inward-facing structures reveal how the transport domain translates and rotates within the framework of the scaffold domain through the transport cycle. Additionally, we propose that DASS transporters ensure substrate coupling by a charge-compensation mechanism, and by structural changes upon substrate release.