+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7p9v | |||||||||||||||||||||||||||||||||
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タイトル | Cryo EM structure of System XC- | |||||||||||||||||||||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / transporter glutamate cystine | |||||||||||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 cystine:glutamate antiporter activity / regulation of neutrophil apoptotic process / L-kynurenine transmembrane transport / L-kynurenine transmembrane transporter activity / regulation of cysteine metabolic process / regulation of glutathione biosynthetic process / regulation of glutamate metabolic process / regulation of melanin biosynthetic process / regulation of AMPA glutamate receptor clustering / L-cystine transport ...cystine:glutamate antiporter activity / regulation of neutrophil apoptotic process / L-kynurenine transmembrane transport / L-kynurenine transmembrane transporter activity / regulation of cysteine metabolic process / regulation of glutathione biosynthetic process / regulation of glutamate metabolic process / regulation of melanin biosynthetic process / regulation of AMPA glutamate receptor clustering / L-cystine transport / negative regulation of ferroptosis / neutral L-amino acid secondary active transmembrane transporter activity / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / methionine transport / tyrosine transport / L-histidine transport / apical pole of neuron / dipeptide import across plasma membrane / aromatic amino acid transmembrane transporter activity / amino acid transport complex / L-amino acid transmembrane transporter activity / : / L-leucine import across plasma membrane / L-alanine transmembrane transporter activity / isoleucine transport / L-alanine import across plasma membrane / phenylalanine transport / valine transport / L-leucine transmembrane transporter activity / amino acid transmembrane transport / regulation of protein transport / calcium:sodium antiporter activity / L-leucine transport / thyroid hormone transport / proline transport / glutathione transmembrane transport / L-glutamate transmembrane transport / regulation of cellular response to oxidative stress / Amino acid transport across the plasma membrane / neutral L-amino acid transmembrane transporter activity / ventricular system development / intracellular glutamate homeostasis / lens fiber cell differentiation / L-glutamate import across plasma membrane / Tryptophan catabolism / striatum development / astrocyte projection / exogenous protein binding / anchoring junction / amino acid transport / limb development / Basigin interactions / response to redox state / microvillus membrane / NFE2L2 regulating anti-oxidant/detoxification enzymes / adult behavior / regulation of synapse organization / lung alveolus development / response to exogenous dsRNA / tryptophan transport / glutathione metabolic process / basal plasma membrane / brush border membrane / response to nicotine / visual learning / modulation of chemical synaptic transmission / response to organic cyclic compound / response to toxic substance / 血小板 / calcium ion transport / double-stranded RNA binding / メラノソーム / virus receptor activity / apical part of cell / cellular response to oxidative stress / regulation of cell population proliferation / basolateral plasma membrane / carbohydrate metabolic process / symbiont entry into host cell / cadherin binding / apical plasma membrane / protein heterodimerization activity / lysosomal membrane / シナプス / 細胞膜 / protein homodimerization activity / RNA binding / extracellular exosome / 核質 / 生体膜 / 細胞膜 類似検索 - 分子機能 | |||||||||||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) | |||||||||||||||||||||||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.4 Å | |||||||||||||||||||||||||||||||||
データ登録者 | Parker, J.L. / Deme, J.C. / Lea, S.M. / Newstead, S. | |||||||||||||||||||||||||||||||||
資金援助 | 英国, 10件
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引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Molecular basis for redox control by the human cystine/glutamate antiporter system xc. 著者: Joanne L Parker / Justin C Deme / Dimitrios Kolokouris / Gabriel Kuteyi / Philip C Biggin / Susan M Lea / Simon Newstead / 要旨: Cysteine plays an essential role in cellular redox homoeostasis as a key constituent of the tripeptide glutathione (GSH). A rate limiting step in cellular GSH synthesis is the availability of ...Cysteine plays an essential role in cellular redox homoeostasis as a key constituent of the tripeptide glutathione (GSH). A rate limiting step in cellular GSH synthesis is the availability of cysteine. However, circulating cysteine exists in the blood as the oxidised di-peptide cystine, requiring specialised transport systems for its import into the cell. System xc is a dedicated cystine transporter, importing cystine in exchange for intracellular glutamate. To counteract elevated levels of reactive oxygen species in cancerous cells system xc is frequently upregulated, making it an attractive target for anticancer therapies. However, the molecular basis for ligand recognition remains elusive, hampering efforts to specifically target this transport system. Here we present the cryo-EM structure of system xc in both the apo and glutamate bound states. Structural comparisons reveal an allosteric mechanism for ligand discrimination, supported by molecular dynamics and cell-based assays, establishing a mechanism for cystine transport in human cells. | |||||||||||||||||||||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7p9v.cif.gz | 173.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7p9v.ent.gz | 138.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7p9v.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/p9/7p9v ftp://data.pdbj.org/pub/pdb/validation_reports/p9/7p9v | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 69161.867 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: SLC3A2, MDU1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P08195 | ||
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#2: タンパク質 | 分子量: 56466.605 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: SLC7A11 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q9UPY5 | ||
#3: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose 研究の焦点であるリガンドがあるか | N | |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: System XC- / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy |
撮影 | 電子線照射量: 59.1 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.18.2_3874: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 300221 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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