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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 6jmq | |||||||||
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タイトル | LAT1-CD98hc complex bound to MEM-108 Fab | |||||||||
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![]() | MEMBRANE PROTEIN/IMMUNE SYSTEM / Transporter / Glycoprotein / Complex / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
機能・相同性 | ![]() L-tryptophan transmembrane transporter activity / alanine transport / L-tryptophan transmembrane transport / positive regulation of L-leucine import across plasma membrane / cellular response to L-arginine / thyroid hormone transmembrane transporter activity / neutral L-amino acid secondary active transmembrane transporter activity / amino acid import across plasma membrane / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / methionine transport ...L-tryptophan transmembrane transporter activity / alanine transport / L-tryptophan transmembrane transport / positive regulation of L-leucine import across plasma membrane / cellular response to L-arginine / thyroid hormone transmembrane transporter activity / neutral L-amino acid secondary active transmembrane transporter activity / amino acid import across plasma membrane / Defective SLC7A7 causes lysinuric protein intolerance (LPI) / methionine transport / tyrosine transport / L-histidine transport / apical pole of neuron / aromatic amino acid transmembrane transporter activity / amino acid transport complex / L-leucine import across plasma membrane / L-alanine transmembrane transporter activity / isoleucine transport / L-alanine import across plasma membrane / L-amino acid transmembrane transporter activity / phenylalanine transport / valine transport / amino acid transmembrane transport / L-leucine transmembrane transporter activity / calcium:sodium antiporter activity / L-leucine transport / thyroid hormone transport / proline transport / positive regulation of cytokine production involved in immune response / negative regulation of vascular associated smooth muscle cell apoptotic process / neutral amino acid transport / amino acid transmembrane transporter activity / external side of apical plasma membrane / Amino acid transport across the plasma membrane / neutral L-amino acid transmembrane transporter activity / Tryptophan catabolism / exogenous protein binding / xenobiotic transport / anchoring junction / response to muscle activity / antiporter activity / Basigin interactions / microvillus membrane / amino acid transport / positive regulation of interleukin-4 production / response to exogenous dsRNA / positive regulation of interleukin-17 production / positive regulation of glial cell proliferation / tryptophan transport / transport across blood-brain barrier / response to hyperoxia / cellular response to glucose starvation / basal plasma membrane / liver regeneration / negative regulation of autophagy / positive regulation of type II interferon production / peptide antigen binding / calcium ion transport / double-stranded RNA binding / virus receptor activity / melanosome / basolateral plasma membrane / cellular response to lipopolysaccharide / carbohydrate metabolic process / cadherin binding / apical plasma membrane / symbiont entry into host cell / protein heterodimerization activity / lysosomal membrane / negative regulation of gene expression / intracellular membrane-bounded organelle / synapse / cell surface / protein homodimerization activity / RNA binding / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
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: 3.31 Å | |||||||||
![]() | Lee, Y. / Nishizawa, T. / Kusakizako, T. / Oda, K. / Ishitani, R. / Nakane, T. / Nureki, O. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc. 著者: Yongchan Lee / Pattama Wiriyasermkul / Chunhuan Jin / Lili Quan / Ryuichi Ohgaki / Suguru Okuda / Tsukasa Kusakizako / Tomohiro Nishizawa / Kazumasa Oda / Ryuichiro Ishitani / Takeshi ...著者: Yongchan Lee / Pattama Wiriyasermkul / Chunhuan Jin / Lili Quan / Ryuichi Ohgaki / Suguru Okuda / Tsukasa Kusakizako / Tomohiro Nishizawa / Kazumasa Oda / Ryuichiro Ishitani / Takeshi Yokoyama / Takanori Nakane / Mikako Shirouzu / Hitoshi Endou / Shushi Nagamori / Yoshikatsu Kanai / Osamu Nureki / ![]() ![]() ![]() 要旨: The L-type amino acid transporter 1 (LAT1 or SLC7A5) transports large neutral amino acids across the membrane and is crucial for brain drug delivery and tumor growth. LAT1 forms a disulfide-linked ...The L-type amino acid transporter 1 (LAT1 or SLC7A5) transports large neutral amino acids across the membrane and is crucial for brain drug delivery and tumor growth. LAT1 forms a disulfide-linked heterodimer with CD98 heavy chain (CD98hc, 4F2hc or SLC3A2), but the mechanism of assembly and amino acid transport are poorly understood. Here we report the cryo-EM structure of the human LAT1-CD98hc heterodimer at 3.3-Å resolution. LAT1 features a canonical Leu T-fold and exhibits an unusual loop structure on transmembrane helix 6, creating an extended cavity that might accommodate bulky amino acids and drugs. CD98hc engages with LAT1 through the extracellular, transmembrane and putative cholesterol-mediated interactions. We also show that two anti-CD98 antibodies recognize distinct, multiple epitopes on CD98hc but not its glycans, explaining their robust reactivities. These results reveal the principles of glycoprotein-solute carrier assembly and provide templates for improving preclinical drugs and antibodies targeting LAT1 or CD98hc. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 235.5 KB | 表示 | ![]() |
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PDB形式 | ![]() | 185.3 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 9849MC ![]() 9850C ![]() 6jmrC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | |
電子顕微鏡画像生データ | ![]() Data #1: Unaligned multi-frame micrographs, Dataset1 [micrographs - multiframe] Data #2: Unaligned multi-frame micrographs, Dataset2 [micrographs - multiframe] Data #3: Micelle subtracted particles used for final reconstruction [picked particles - single frame - processed]) |
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 2種, 2分子 AB
#1: タンパク質 | 分子量: 56043.746 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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#2: タンパク質 | 分子量: 68069.625 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
-抗体 , 2種, 2分子 CD
#3: 抗体 | 分子量: 22577.857 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() |
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#4: 抗体 | 分子量: 23227.152 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() |
-糖 , 2種, 4分子 ![](data/chem/img/NAG.gif)
#5: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
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#7: 糖 |
-非ポリマー , 1種, 5分子 ![](data/chem/img/CLR.gif)
#6: 化合物 | ChemComp-CLR / |
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-詳細
配列の詳細 | Authors do not know the actual sequences of chains C, D since the protein WAS derived from an ...Authors do not know the actual sequences of chains C, D since the protein WAS derived from an commercial antibody whose sequence is NOT available. |
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-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 |
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試料調製
構成要素 | 名称: LAT1-CD98hc complex bound to MEM-108 Fab / タイプ: COMPLEX / Entity ID: #1-#4 / 由来: MULTIPLE SOURCES |
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分子量 | 値: 175 kDa/nm / 実験値: YES |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
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 |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 7.14 e/Å2 フィルム・検出器のモデル: FEI FALCON III (4k x 4k) |
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解析
ソフトウェア |
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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: 3.31 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 250712 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 立体化学のターゲット値: CDL v1.2 | ||||||||||||||||||||||||
拘束条件 |
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