+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6d04 | |||||||||
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タイトル | Cryo-EM structure of a Plasmodium vivax invasion complex essential for entry into human reticulocytes; two molecules of parasite ligand, subclass 1. | |||||||||
要素 |
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キーワード | CELL INVASION / malaria / Plasmodium vivax / reticulocyte / invasion | |||||||||
機能・相同性 | 機能・相同性情報 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 / Differentiation of keratinocytes in interfollicular epidermis in mammalian skin / positive regulation of cell motility ...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 / Differentiation of keratinocytes in interfollicular epidermis in mammalian skin / positive regulation of cell motility / response to copper ion / response to iron ion / RND1 GTPase cycle / response to manganese ion / RND2 GTPase cycle / positive regulation of bone resorption / RHOB GTPase cycle / Golgi Associated Vesicle Biogenesis / RHOC GTPase cycle / RHOJ GTPase cycle / RHOQ GTPase cycle / positive regulation of phosphorylation / CDC42 GTPase cycle / RHOH GTPase cycle / endocytic vesicle / RHOG GTPase cycle / transport across blood-brain barrier / RHOA GTPase cycle / RAC2 GTPase cycle / RAC3 GTPase cycle / basal plasma membrane / response to nutrient / response to retinoic acid / positive regulation of T cell proliferation / clathrin-coated pit / positive regulation of B cell proliferation / Hsp70 protein binding / RAC1 GTPase cycle / ERK1 and ERK2 cascade / ferric iron binding / osteoclast differentiation / clathrin-coated endocytic vesicle membrane / cellular response to leukemia inhibitory factor / actin filament organization / acute-phase response / cellular response to iron ion / Post-translational protein phosphorylation / Iron uptake and transport / ferrous iron binding / positive regulation of protein-containing complex assembly / regulation of protein stability / regulation of iron ion transport / HFE-transferrin receptor complex / recycling endosome / receptor internalization / positive regulation of receptor-mediated endocytosis / positive regulation of protein localization to nucleus / cellular response to xenobiotic stimulus / recycling endosome membrane / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / Cargo recognition for clathrin-mediated endocytosis / positive regulation of peptidyl-serine phosphorylation / double-stranded RNA binding / extracellular vesicle / Clathrin-mediated endocytosis / virus receptor activity / melanosome / late endosome / Platelet degranulation / positive regulation of NF-kappaB transcription factor activity / positive regulation of canonical NF-kappaB signal transduction / iron ion transport / antibacterial humoral response / basolateral plasma membrane / cytoplasmic vesicle / secretory granule lumen / intracellular iron ion homeostasis / vesicle / blood microparticle / endosome / endosome membrane / early endosome / response to hypoxia / intracellular signal transduction / positive regulation of protein phosphorylation / apical plasma membrane / endoplasmic reticulum lumen / external side of plasma membrane / intracellular membrane-bounded organelle / positive regulation of gene expression / positive regulation of DNA-templated transcription / negative regulation of apoptotic process / protein-containing complex binding / protein kinase binding / perinuclear region of cytoplasm / cell surface / protein homodimerization activity / RNA binding / extracellular space / extracellular exosome 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) Plasmodium vivax (マラリア 病原虫) | |||||||||
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: 3.74 Å | |||||||||
データ登録者 | Gruszczyk, J. / Huang, R.K. / Hong, C. / Yu, Z. / Tham, W.H. | |||||||||
引用 | ジャーナル: Nature / 年: 2018 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. | |||||||||
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 | 6d04.cif.gz | 637 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6d04.ent.gz | 523.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6d04.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 | 6d04_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6d04_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 6d04_validation.xml.gz | 90.9 KB | 表示 | |
CIF形式データ | 6d04_validation.cif.gz | 140 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/d0/6d04 ftp://data.pdbj.org/pub/pdb/validation_reports/d0/6d04 | HTTPS FTP |
-関連構造データ
関連構造データ | 7784MC 7783C 7785C 6bpaC 6bpbC 6bpcC 6bpdC 6bpeC 6d03C 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 (文献) |
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類似構造データ |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-タンパク質 , 3種, 6分子 ABCDEF
#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) Homo sapiens (ヒト) / 遺伝子: TFRC / 細胞株 (発現宿主): Sf21 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 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) Homo sapiens (ヒト) / 参照: UniProt: P02787 #3: タンパク質 | 分子量: 96798.477 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) Plasmodium vivax (マラリア 病原虫) 株: Salvador I / 遺伝子: PVX_094255 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: A5K736 |
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-糖 , 2種, 10分子
#4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #6: 糖 | ChemComp-NAG / |
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-非ポリマー , 3種, 10分子
#5: 化合物 | #7: 化合物 | ChemComp-FE / #8: 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 |
-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: two molecules of parasite ligand, subclass 1 / Entity ID: #1-#3 / 由来: MULTIPLE SOURCES | ||||||||||||||||
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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 | ||||||||||||||||
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 | ||||||||||||||||
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 | 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 |
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 |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
3次元再構成 | 解像度: 3.74 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 287253 / 対称性のタイプ: POINT |