+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6irt | |||||||||||||||||||||
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タイトル | human LAT1-4F2hc complex bound with BCH | |||||||||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / transporter | |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 neutral L-amino acid secondary active transmembrane transporter activity / tyrosine transport / L-histidine transport / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / aromatic amino acid transmembrane transporter activity / methionine transport / apical pole of neuron / amino acid transport complex / L-leucine import across plasma membrane / isoleucine transport ...neutral L-amino acid secondary active transmembrane transporter activity / tyrosine transport / L-histidine transport / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / aromatic amino acid transmembrane transporter activity / methionine transport / apical pole of neuron / amino acid transport complex / L-leucine import across plasma membrane / isoleucine transport / L-alanine transmembrane transporter activity / L-leucine transmembrane transporter activity / L-alanine import across plasma membrane / phenylalanine transport / valine transport / L-leucine transport / calcium:sodium antiporter activity / thyroid hormone transport / proline transport / Amino acid transport across the plasma membrane / neutral L-amino acid transmembrane transporter activity / Tryptophan catabolism / exogenous protein binding / anchoring junction / Basigin interactions / amino acid transport / response to exogenous dsRNA / tryptophan transport / basal plasma membrane / calcium ion transport / double-stranded RNA binding / melanosome / virus receptor activity / basolateral plasma membrane / carbohydrate metabolic process / cadherin binding / symbiont entry into host cell / apical plasma membrane / protein heterodimerization activity / lysosomal membrane / synapse / cell surface / protein homodimerization activity / RNA binding / extracellular exosome / nucleoplasm / membrane / plasma membrane 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: 3.5 Å | |||||||||||||||||||||
データ登録者 | Yan, R.H. / Zhao, X. / Lei, J.L. / Zhou, Q. | |||||||||||||||||||||
資金援助 | 中国, 6件
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引用 | ジャーナル: Nature / 年: 2019 タイトル: Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex. 著者: Renhong Yan / Xin Zhao / Jianlin Lei / Qiang Zhou / 要旨: The L-type amino acid transporter 1 (LAT1; also known as SLC7A5) catalyses the cross-membrane flux of large neutral amino acids in a sodium- and pH-independent manner. LAT1, an antiporter of the ...The L-type amino acid transporter 1 (LAT1; also known as SLC7A5) catalyses the cross-membrane flux of large neutral amino acids in a sodium- and pH-independent manner. LAT1, an antiporter of the amino acid-polyamine-organocation superfamily, also catalyses the permeation of thyroid hormones, pharmaceutical drugs, and hormone precursors such as L-3,4-dihydroxyphenylalanine across membranes. Overexpression of LAT1 has been observed in a wide range of tumour cells, and it is thus a potential target for anti-cancer drugs. LAT1 forms a heteromeric amino acid transporter complex with 4F2 cell-surface antigen heavy chain (4F2hc; also known as SLC3A2)-a type II membrane glycoprotein that is essential for the stability of LAT1 and for its localization to the plasma membrane. Despite extensive cell-based characterization of the LAT1-4F2hc complex and structural determination of its homologues in bacteria, the interactions between LAT1 and 4F2hc and the working mechanism of the complex remain largely unknown. Here we report the cryo-electron microscopy structures of human LAT1-4F2hc alone and in complex with the inhibitor 2-amino-2-norbornanecarboxylic acid at resolutions of 3.3 Å and 3.5 Å, respectively. LAT1 exhibits an inward open conformation. Besides a disulfide bond association, LAT1 also interacts extensively with 4F2hc on the extracellular side, within the membrane, and on the intracellular side. Biochemical analysis reveals that 4F2hc is essential for the transport activity of the complex. Together, our characterizations shed light on the architecture of the LAT1-4F2hc complex, and provide insights into its function and the mechanisms through which it might be associated with disease. | |||||||||||||||||||||
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 | 6irt.cif.gz | 177 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6irt.ent.gz | 138.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6irt.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
文書・要旨 | 6irt_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6irt_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 6irt_validation.xml.gz | 38.6 KB | 表示 | |
CIF形式データ | 6irt_validation.cif.gz | 57 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ir/6irt ftp://data.pdbj.org/pub/pdb/validation_reports/ir/6irt | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 70160.828 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, hCG_2016598 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: J3KPF3 | ||||||
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#2: タンパク質 | 分子量: 57244.934 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: SLC7A5, CD98LC, LAT1, MPE16 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q01650 | ||||||
#3: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #4: 化合物 | #5: 化合物 | ChemComp-AUU / ( | 配列の詳細 | Unexpected variation that may be derived from the cDNA library used for subcloning or PCR error | |
-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: human LAT1-4F2hc complex bound with BCH / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
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分子量 | 値: 0.1 MDa / 実験値: NO |
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: 8 |
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 FIELD |
撮影 | 電子線照射量: 48 e/Å2 フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.11.1_2575: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 1247297 | ||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 262949 / アルゴリズム: FOURIER SPACE / クラス平均像の数: 1 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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