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基本情報
登録情報 | データベース: PDB / ID: 6d03 | |||||||||
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タイトル | Cryo-EM structure of a Plasmodium vivax invasion complex essential for entry into human reticulocytes; one molecule of parasite ligand. | |||||||||
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![]() | CELL INVASION / malaria / Plasmodium vivax / reticulocyte / invasion | |||||||||
機能・相同性 | ![]() transferrin receptor activity / negative regulation of mitochondrial fusion / transferrin transport / iron chaperone activity / Transferrin endocytosis and recycling / transferrin receptor binding / positive regulation of isotype switching / basal part of cell / positive regulation of cell motility / response to copper ion ...transferrin receptor activity / negative regulation of mitochondrial fusion / transferrin transport / iron chaperone activity / Transferrin endocytosis and recycling / transferrin receptor binding / positive regulation of isotype switching / basal part of cell / positive regulation of cell motility / response to copper ion / response to iron ion / response to manganese ion / RND1 GTPase cycle / RND2 GTPase cycle / RHOB GTPase cycle / Golgi Associated Vesicle Biogenesis / RHOJ GTPase cycle / RHOC GTPase cycle / RHOQ GTPase cycle / CDC42 GTPase cycle / RHOH GTPase cycle / transport across blood-brain barrier / RHOG GTPase cycle / endocytic vesicle / RHOA GTPase cycle / RAC2 GTPase cycle / RAC3 GTPase cycle / positive regulation of bone resorption / response to retinoic acid / positive regulation of T cell proliferation / clathrin-coated pit / positive regulation of phosphorylation / positive regulation of B cell proliferation / Hsp70 protein binding / RAC1 GTPase cycle / ERK1 and ERK2 cascade / response to nutrient / ferric iron binding / osteoclast differentiation / basal plasma membrane / cellular response to leukemia inhibitory factor / acute-phase response / cellular response to iron ion / actin filament organization / Iron uptake and transport / Post-translational protein phosphorylation / clathrin-coated endocytic vesicle membrane / positive regulation of protein-containing complex assembly / regulation of protein stability / ferrous iron binding / regulation of iron ion transport / HFE-transferrin receptor complex / receptor internalization / recycling endosome / positive regulation of receptor-mediated endocytosis / positive regulation of protein localization to nucleus / recycling endosome membrane / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / double-stranded RNA binding / extracellular vesicle / melanosome / cellular response to xenobiotic stimulus / late endosome / Cargo recognition for clathrin-mediated endocytosis / Platelet degranulation / positive regulation of peptidyl-serine phosphorylation / Clathrin-mediated endocytosis / virus receptor activity / positive regulation of NF-kappaB transcription factor activity / iron ion transport / antibacterial humoral response / cytoplasmic vesicle / basolateral plasma membrane / secretory granule lumen / positive regulation of canonical NF-kappaB signal transduction / intracellular iron ion homeostasis / vesicle / early endosome / blood microparticle / endosome membrane / response to hypoxia / intracellular signal transduction / endosome / positive regulation of protein phosphorylation / apical plasma membrane / endoplasmic reticulum lumen / external side of plasma membrane / intracellular membrane-bounded organelle / protein-containing complex binding / positive regulation of gene expression / negative regulation of apoptotic process / protein kinase binding / positive regulation of DNA-templated transcription / perinuclear region of cytoplasm / cell surface / protein homodimerization activity / RNA binding / extracellular space / extracellular exosome / extracellular region 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: 3.68 Å | |||||||||
![]() | Gruszczyk, J. / Huang, R.K. / Hong, C. / Yu, Z. / Tham, W.H. | |||||||||
![]() | ![]() タイトル: Cryo-EM structure of an essential Plasmodium vivax invasion complex. 著者: Jakub Gruszczyk / Rick K Huang / Li-Jin Chan / Sébastien Menant / Chuan Hong / James M Murphy / Yee-Foong Mok / Michael D W Griffin / Richard D Pearson / Wilson Wong / Alan F Cowman / ...著者: Jakub Gruszczyk / Rick K Huang / Li-Jin Chan / Sébastien Menant / Chuan Hong / James M Murphy / Yee-Foong Mok / Michael D W Griffin / Richard D Pearson / Wilson Wong / Alan F Cowman / Zhiheng Yu / Wai-Hong Tham / ![]() ![]() ![]() 要旨: Plasmodium vivax is the most widely distributed malaria parasite that infects humans. P. vivax invades reticulocytes exclusively, and successful entry depends on specific interactions between the P. ...Plasmodium vivax is the most widely distributed malaria parasite that infects humans. P. vivax invades reticulocytes exclusively, and successful entry depends on specific interactions between the P. vivax reticulocyte-binding protein 2b (PvRBP2b) and transferrin receptor 1 (TfR1). TfR1-deficient erythroid cells are refractory to invasion by P. vivax, and anti-PvRBP2b monoclonal antibodies inhibit reticulocyte binding and block P. vivax invasion in field isolates. Here we report a high-resolution cryo-electron microscopy structure of a ternary complex of PvRBP2b bound to human TfR1 and transferrin, at 3.7 Å resolution. Mutational analyses show that PvRBP2b residues involved in complex formation are conserved; this suggests that antigens could be designed that act across P. vivax strains. Functional analyses of TfR1 highlight how P. vivax hijacks TfR1, an essential housekeeping protein, by binding to sites that govern host specificity, without affecting its cellular function of transporting iron. Crystal and solution structures of PvRBP2b in complex with antibody fragments characterize the inhibitory epitopes. Our results establish a structural framework for understanding how P. vivax reticulocyte-binding protein engages its receptor and the molecular mechanism of inhibitory monoclonal antibodies, providing important information for the design of novel vaccine candidates. | |||||||||
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構造の表示
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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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PDBx/mmCIF形式 | ![]() | 554.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 452.4 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.2 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.2 MB | 表示 | |
XML形式データ | ![]() | 81.4 KB | 表示 | |
CIF形式データ | ![]() | 123.6 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 7783MC ![]() 7784C ![]() 7785C ![]() 6bpaC ![]() 6bpbC ![]() 6bpcC ![]() 6bpdC ![]() 6bpeC ![]() 6d04C ![]() 6d05C 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 |
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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 , 3種, 5分子 ABCDE
#1: タンパク質 | 分子量: 73940.477 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P02786 #2: タンパク質 | 分子量: 77153.906 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() #3: タンパク質 | | 分子量: 96798.477 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 株: Salvador I / 遺伝子: PVX_094255 / 発現宿主: ![]() ![]() |
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-糖 , 3種, 10分子 ![](data/chem/img/NAG.gif)
#4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(2-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #7: 糖 | ChemComp-NAG / |
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-非ポリマー , 3種, 10分子 ![](data/chem/img/CA.gif)
![](data/chem/img/FE.gif)
![](data/chem/img/CO3.gif)
![](data/chem/img/FE.gif)
![](data/chem/img/CO3.gif)
#6: 化合物 | #8: 化合物 | ChemComp-FE / #9: 化合物 | ChemComp-CO3 / |
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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: ternary complex between human transferrin receptor 1, transferrin and Plasmodium vivax reticulocyte-binding protein 2b タイプ: COMPLEX / 詳細: one molecule of parasite ligand / Entity ID: #1-#3 / 由来: MULTIPLE SOURCES | ||||||||||||||||
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由来(天然) | 生物種: ![]() | ||||||||||||||||
由来(組換発現) | 生物種: ![]() | ||||||||||||||||
緩衝液 | pH: 7.5 | ||||||||||||||||
緩衝液成分 |
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試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 400 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 | ||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K |
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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 / 倍率(公称値): 81000 X / 倍率(補正後): 37037 X / Cs: 0.01 mm / アライメント法: ZEMLIN TABLEAU |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 15 sec. / 電子線照射量: 80 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 撮影したグリッド数: 1 |
電子光学装置 | エネルギーフィルター名称: GIF Quantum LS 球面収差補正装置: A Cs corrector with two hexapole elements is operated immediately underneath the objective lens to reduce the 3rd order spherical aberration. |
画像スキャン | サンプリングサイズ: 5 µm / 動画フレーム数/画像: 50 |
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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: 2000 | ||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.68 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 637649 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||
拘束条件 |
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