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基本情報
登録情報 | データベース: EMDB / ID: EMD-7785 | |||||||||
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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 2. | |||||||||
![]() | Structural insight into specificity of human malaria parasite Plasmodium vivax towards reticulocytes; two molecules of parasite ligand, subclass 2. | |||||||||
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![]() | malaria / Plasmodium vivax / reticulocyte / invasion / CELL INVASION | |||||||||
機能・相同性 | ![]() transferrin receptor activity / postsynaptic recycling endosome membrane / negative regulation of mitochondrial fusion / iron chaperone activity / transferrin transport / transferrin receptor binding / Transferrin endocytosis and recycling / positive regulation of isotype switching / basal part of cell / response to copper ion ...transferrin receptor activity / postsynaptic recycling endosome membrane / negative regulation of mitochondrial fusion / iron chaperone activity / transferrin transport / transferrin receptor binding / Transferrin endocytosis and recycling / positive regulation of isotype switching / basal part of cell / response to copper ion / Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin / response to iron ion / response to manganese ion / RND1 GTPase cycle / RND2 GTPase cycle / positive regulation of cell motility / RHOB GTPase cycle / Golgi Associated Vesicle Biogenesis / RHOC GTPase cycle / RHOJ GTPase cycle / RHOQ GTPase cycle / CDC42 GTPase cycle / RHOH GTPase cycle / RHOG GTPase cycle / endocytic vesicle / RHOA GTPase cycle / RAC2 GTPase cycle / RAC3 GTPase cycle / positive regulation of bone resorption / regulation of postsynaptic membrane neurotransmitter receptor levels / transport across blood-brain barrier / response to retinoic acid / positive regulation of phosphorylation / positive regulation of T cell proliferation / clathrin-coated pit / positive regulation of B cell proliferation / RAC1 GTPase cycle / response to nutrient / ERK1 and ERK2 cascade / Hsp70 protein binding / ferric iron binding / osteoclast differentiation / cellular response to leukemia inhibitory factor / actin filament organization / basal plasma membrane / acute-phase response / cellular response to iron ion / Post-translational protein phosphorylation / positive regulation of protein-containing complex assembly / clathrin-coated endocytic vesicle membrane / Iron uptake and transport / regulation of iron ion transport / HFE-transferrin receptor complex / ferrous iron binding / regulation of protein stability / recycling endosome / receptor internalization / positive regulation of receptor-mediated endocytosis / positive regulation of protein localization to nucleus / multicellular organismal-level iron ion homeostasis / recycling endosome membrane / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / antibacterial humoral response / late endosome / melanosome / Platelet degranulation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / cellular response to xenobiotic stimulus / Cargo recognition for clathrin-mediated endocytosis / extracellular vesicle / double-stranded RNA binding / Clathrin-mediated endocytosis / iron ion transport / virus receptor activity / cytoplasmic vesicle / basolateral plasma membrane / secretory granule lumen / vesicle / blood microparticle / transmembrane transporter binding / intracellular iron ion homeostasis / positive regulation of canonical NF-kappaB signal transduction / early endosome / response to hypoxia / endosome / endosome membrane / intracellular signal transduction / apical plasma membrane / endoplasmic reticulum lumen / external side of plasma membrane / intracellular membrane-bounded organelle / positive regulation of gene expression / protein-containing complex binding / negative regulation of apoptotic process / protein kinase binding / positive regulation of DNA-templated transcription / perinuclear region of cytoplasm / glutamatergic synapse / enzyme binding / cell surface 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.8 Å | |||||||||
![]() | Gruszczyk J / Huang RK | |||||||||
![]() | ![]() 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 | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16 KB 16 KB | 表示 表示 | ![]() |
画像 | ![]() | 68.6 KB | ||
Filedesc metadata | ![]() | 7.2 KB | ||
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 | ![]() 6d05MC ![]() 7783C ![]() 7784C ![]() 6bpaC ![]() 6bpbC ![]() 6bpcC ![]() 6bpdC ![]() 6bpeC ![]() 6d03C ![]() 6d04C M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ |
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Structural insight into specificity of human malaria parasite Plasmodium vivax towards reticulocytes; two molecules of parasite ligand, subclass 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.35 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : ternary complex between human transferrin receptor 1, transferrin...
全体 | 名称: ternary complex between human transferrin receptor 1, transferrin and Plasmodium vivax reticulocyte-binding protein 2b |
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要素 |
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-超分子 #1: ternary complex between human transferrin receptor 1, transferrin...
超分子 | 名称: ternary complex between human transferrin receptor 1, transferrin and Plasmodium vivax reticulocyte-binding protein 2b タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 / 詳細: two molecules of parasite ligand, subclass 2 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Transferrin receptor protein 1
分子 | 名称: Transferrin receptor protein 1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 73.940477 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: ADPHHHHHHS SGIEGRGEFR LYWDDLKRKL SEKLDSTDFT STIKLLNENS YVPREAGSQK DENLALYVEN QFREFKLSKV WRDQHFVKI QVKDSAQNSV IIVDKNGRLV YLVENPGGYV AYSKAATVTG KLVHANFGTK KDFEDLYTPV NGSIVIVRAG K ITFAEKVA ...文字列: ADPHHHHHHS SGIEGRGEFR LYWDDLKRKL SEKLDSTDFT STIKLLNENS YVPREAGSQK DENLALYVEN QFREFKLSKV WRDQHFVKI QVKDSAQNSV IIVDKNGRLV YLVENPGGYV AYSKAATVTG KLVHANFGTK KDFEDLYTPV NGSIVIVRAG K ITFAEKVA NAESLNAIGV LIYMDQTKFP IVNAELSFFG HAHLGTGDPY TPGFPSFNHT QFPPSRSSGL PNIPVQTISR AA AEKLFGN MEGDCPSDWK TDSTCRMVTS ESKNVKLTVS NVLKEIKILN IFGVIKGFVE PDHYVVVGAQ RDAWGPGAAK SGV GTALLL KLAQMFSDMV LKDGFQPSRS IIFASWSAGD FGSVGATEWL EGYLSSLHLK AFTYINLDKA VLGTSNFKVS ASPL LYTLI EKTMQNVKHP VTGQFLYQDS NWASKVEKLT LDNAAFPFLA YSGIPAVSFC FCEDTDYPYL GTTMDTYKEL IERIP ELNK VARAAAEVAG QFVIKLTHDV ELNLDYERYN SQLLSFVRDL NQYRADIKEM GLSLQWLYSA RGDFFRATSR LTTDFG NAE KTDRFVMKKL NDRVMRVEYH FLSPYVSPKE SPFRHVFWGS GSHTLPALLE NLKLRKQNNG AFNETLFRNQ LALATWT IQ GAANALSGDV WDIDNEF UniProtKB: Transferrin receptor protein 1 |
-分子 #2: Serotransferrin
分子 | 名称: Serotransferrin / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 77.153906 KDa |
配列 | 文字列: MRLAVGALLV CAVLGLCLAV PDKTVRWCAV SEHEATKCQS FRDHMKSVIP SDGPSVACVK KASYLDCIRA IAANEADAVT LDAGLVYDA YLAPNNLKPV VAEFYGSKED PQTFYYAVAV VKKDSGFQMN QLRGKKSCHT GLGRSAGWNI PIGLLYCDLP E PRKPLEKA ...文字列: MRLAVGALLV CAVLGLCLAV PDKTVRWCAV SEHEATKCQS FRDHMKSVIP SDGPSVACVK KASYLDCIRA IAANEADAVT LDAGLVYDA YLAPNNLKPV VAEFYGSKED PQTFYYAVAV VKKDSGFQMN QLRGKKSCHT GLGRSAGWNI PIGLLYCDLP E PRKPLEKA VANFFSGSCA PCADGTDFPQ LCQLCPGCGC STLNQYFGYS GAFKCLKDGA GDVAFVKHST IFENLANKAD RD QYELLCL DNTRKPVDEY KDCHLAQVPS HTVVARSMGG KEDLIWELLN QAQEHFGKDK SKEFQLFSSP HGKDLLFKDS AHG FLKVPP RMDAKMYLGY EYVTAIRNLR EGTCPEAPTD ECKPVKWCAL SHHERLKCDE WSVNSVGKIE CVSAETTEDC IAKI MNGEA DAMSLDGGFV YIAGKCGLVP VLAENYNKSD NCEDTPEAGY FAVAVVKKSA SDLTWDNLKG KKSCHTAVGR TAGWN IPMG LLYNKINHCR FDEFFSEGCA PGSKKDSSLC KLCMGSGLNL CEPNNKEGYY GYTGAFRCLV EKGDVAFVKH QTVPQN TGG KNPDPWAKNL NEKDYELLCL DGTRKPVEEY ANCHLARAPN HAVVTRKDKE ACVHKILRQQ QHLFGSNVTD CSGNFCL FR SETKDLLFRD DTVCLAKLHD RNTYEKYLGE EYVKAVGNLR KCSTSSLLEA CTFRRP UniProtKB: Serotransferrin |
-分子 #3: Reticulocyte binding protein 2, putative
分子 | 名称: Reticulocyte binding protein 2, putative / タイプ: protein_or_peptide / ID: 3 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 96.798477 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: GAMGSMHIPI QPSPESTQST NTTDNIDYFD ISDESNYYLI SQLRPHFSNI YFFDEFKRYA SYHTEIKRYE DIHKTKVNSL LNEASRAIG ICNRAKNTVK GLINILENPQ KFKTQRESYD VKLRQYEEKK EAFRGCLLNK NRKNLDQIKK INNEIRDLLE K LKCSQDCQ ...文字列: GAMGSMHIPI QPSPESTQST NTTDNIDYFD ISDESNYYLI SQLRPHFSNI YFFDEFKRYA SYHTEIKRYE DIHKTKVNSL LNEASRAIG ICNRAKNTVK GLINILENPQ KFKTQRESYD VKLRQYEEKK EAFRGCLLNK NRKNLDQIKK INNEIRDLLE K LKCSQDCQ TNVYFDMIKI YLVDFKKMPY ENYDTFIKQY KNSYLSGVDM IRKIEKQIDN PVTINAIKFT QKEMGYIIDR FE YHLQKVK HSIDQVTALS DGVKPKQVTK NRLKEYYFNI GNYYSIFKFG KDSLNMLNKA LIHKEKIVHN LLGELFGHLE ERI SKLIDS EYFITESNNI ISQSEETLKL AEDVYDKNTK LIEDLTLYPH LEINEFKKDY DNNVEDLRES IIYIQSYVSS IKSA YRYNV LEKDSVESKQ KNIPANSNAQ KKVDELLSII DSISYSNFSV AENFQKMKDY YKEIEKLKIK ILQLIEAIKK YQQHV EELI NKEKAVAILK EDINKIIEYI KGIIEKLKQL ISANKDFDKI FQQVEQLINE ALFNKDQFEH NKNDLHTKMK EIMHTF HER DLQQFLDNMS KFLKDQEASY QNADSKEKLD QLLTTVKAKQ DELKEMKCDD IPDIIDNLKK ESQNVLNLKD EVINKQF EN MRTEMSSSLD QMTKEYNALK SSIEEYEAEK KGIENHKQNI IKRKNTFIVA EHENDEDVPE GKNTYNEFIS NKDTILQK E SAISNQMNTL EEKKRNRKTT LQTYGDAIQK LETYTEKKDE ETKVLLDKFN TEVENFKLDE DEKSFNDAKS IVSNTINEV ENENKNIDSI KKVNIAMKRS UniProtKB: Reticulocyte binding protein 2, putative |
-分子 #5: CALCIUM ION
分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 5 / コピー数: 2 / 式: CA |
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分子量 | 理論値: 40.078 Da |
-分子 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 6 / コピー数: 4 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-分子 #7: FE (III) ION
分子 | 名称: FE (III) ION / タイプ: ligand / ID: 7 / コピー数: 4 / 式: FE |
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分子量 | 理論値: 55.845 Da |
-分子 #8: CARBONATE ION
分子 | 名称: CARBONATE ION / タイプ: ligand / ID: 8 / コピー数: 4 / 式: CO3 |
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分子量 | 理論値: 60.009 Da |
Chemical component information | ![]() ChemComp-CO3: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.5 構成要素:
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | 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 / 平均露光時間: 15.0 sec. / 平均電子線量: 80.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 想定した対称性 - 点群: C2 (2回回転対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION / 使用した粒子像数: 302858 |
初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: PROJECTION MATCHING |