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- EMDB-7783: Cryo-EM structure of a Plasmodium vivax invasion complex essentia... -
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Basic information
Entry | Database: EMDB / ID: EMD-7783 | |||||||||
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Title | Cryo-EM structure of a Plasmodium vivax invasion complex essential for entry into human reticulocytes; one molecule of parasite ligand. | |||||||||
![]() | Structural insight into specificity of human malaria parasite Plasmodium vivax towards reticulocytes; one molecule of parasite ligand. | |||||||||
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Function / homology | ![]() 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 / RHOB GTPase cycle / Golgi Associated Vesicle Biogenesis / RHOC GTPase cycle / RHOJ GTPase cycle / RHOQ GTPase cycle / CDC42 GTPase cycle / RHOH GTPase cycle / endocytic vesicle / RHOG GTPase cycle / transport across blood-brain barrier / RHOA GTPase cycle / RAC2 GTPase cycle / positive regulation of bone resorption / RAC3 GTPase cycle / response to retinoic acid / positive regulation of T cell proliferation / clathrin-coated pit / positive regulation of B cell proliferation / positive regulation of phosphorylation / Hsp70 protein binding / RAC1 GTPase cycle / ERK1 and ERK2 cascade / ferric iron binding / osteoclast differentiation / response to nutrient / basal plasma 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 / clathrin-coated endocytic vesicle membrane / 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 / 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 / blood microparticle / early endosome / response to hypoxia / endosome membrane / intracellular signal transduction / endosome / 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 / protein-containing complex binding / negative regulation of apoptotic process / protein kinase binding / perinuclear region of cytoplasm / positive regulation of DNA-templated transcription / cell surface / protein homodimerization activity / RNA binding / extracellular space / extracellular exosome Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.68 Å | |||||||||
![]() | Gruszczyk J / Huang RK / Hong C / Yu Z / Tham WH | |||||||||
![]() | ![]() Title: Cryo-EM structure of an essential Plasmodium vivax invasion complex. Authors: 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 / ...Authors: 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 / ![]() ![]() ![]() Abstract: 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. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 2.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.4 KB 19.4 KB | Display Display | ![]() |
Images | ![]() | 166.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6d03MC ![]() 7784C ![]() 7785C ![]() 6bpaC ![]() 6bpbC ![]() 6bpcC ![]() 6bpdC ![]() 6bpeC ![]() 6d04C ![]() 6d05C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Structural insight into specificity of human malaria parasite Plasmodium vivax towards reticulocytes; one molecule of parasite ligand. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.35 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : ternary complex between human transferrin receptor 1, transferrin...
Entire | Name: ternary complex between human transferrin receptor 1, transferrin and Plasmodium vivax reticulocyte-binding protein 2b |
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Components |
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-Supramolecule #1: ternary complex between human transferrin receptor 1, transferrin...
Supramolecule | Name: ternary complex between human transferrin receptor 1, transferrin and Plasmodium vivax reticulocyte-binding protein 2b type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 / Details: one molecule of parasite ligand |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Transferrin receptor protein 1
Macromolecule | Name: Transferrin receptor protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 73.940477 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: ADPHHHHHHS SGIEGRGEFR LYWDDLKRKL SEKLDSTDFT STIKLLNENS YVPREAGSQK DENLALYVEN QFREFKLSKV WRDQHFVKI QVKDSAQNSV IIVDKNGRLV YLVENPGGYV AYSKAATVTG KLVHANFGTK KDFEDLYTPV NGSIVIVRAG K ITFAEKVA ...String: 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 |
-Macromolecule #2: Serotransferrin
Macromolecule | Name: Serotransferrin / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 77.153906 KDa |
Sequence | String: MRLAVGALLV CAVLGLCLAV PDKTVRWCAV SEHEATKCQS FRDHMKSVIP SDGPSVACVK KASYLDCIRA IAANEADAVT LDAGLVYDA YLAPNNLKPV VAEFYGSKED PQTFYYAVAV VKKDSGFQMN QLRGKKSCHT GLGRSAGWNI PIGLLYCDLP E PRKPLEKA ...String: 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 |
-Macromolecule #3: Reticulocyte binding protein 2, putative
Macromolecule | Name: Reticulocyte binding protein 2, putative / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 96.798477 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GAMGSMHIPI QPSPESTQST NTTDNIDYFD ISDESNYYLI SQLRPHFSNI YFFDEFKRYA SYHTEIKRYE DIHKTKVNSL LNEASRAIG ICNRAKNTVK GLINILENPQ KFKTQRESYD VKLRQYEEKK EAFRGCLLNK NRKNLDQIKK INNEIRDLLE K LKCSQDCQ ...String: 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 |
-Macromolecule #6: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 4 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #8: FE (III) ION
Macromolecule | Name: FE (III) ION / type: ligand / ID: 8 / Number of copies: 4 / Formula: FE |
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Molecular weight | Theoretical: 55.845 Da |
-Macromolecule #9: CARBONATE ION
Macromolecule | Name: CARBONATE ION / type: ligand / ID: 9 / Number of copies: 4 / Formula: CO3 |
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Molecular weight | Theoretical: 60.009 Da |
Chemical component information | ![]() ChemComp-CO3: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Pretreatment - Type: GLOW DISCHARGE | ||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Spherical aberration corrector: A Cs corrector with two hexapole elements is operated immediately underneath the objective lens to reduce the 3rd order spherical aberration. Energy filter - Name: GIF Quantum LS |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Sampling interval: 5.0 µm / Number grids imaged: 1 / Average exposure time: 15.0 sec. / Average electron dose: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Calibrated magnification: 37037 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 0.01 mm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |