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Yorodumi- PDB-6d05: Cryo-EM structure of a Plasmodium vivax invasion complex essentia... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6d05 | |||||||||
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Title | Cryo-EM structure of a Plasmodium vivax invasion complex essential for entry into human reticulocytes; two molecules of parasite ligand, subclass 2. | |||||||||
Components |
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Keywords | CELL INVASION / malaria / Plasmodium vivax / reticulocyte / invasion | |||||||||
Function / homology | Function and homology information 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 iron 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 iron ion / response to copper 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 / RHOH GTPase cycle / CDC42 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 B cell proliferation / positive regulation of phosphorylation / Hsp70 protein binding / RAC1 GTPase cycle / ERK1 and ERK2 cascade / response to nutrient / ferric iron binding / basal plasma membrane / osteoclast differentiation / cellular response to leukemia inhibitory factor / acute-phase response / actin filament organization / Iron uptake and transport / Post-translational protein phosphorylation / ferrous iron binding / clathrin-coated endocytic vesicle membrane / positive regulation of protein-containing complex assembly / regulation of protein stability / regulation of iron ion transport / HFE-transferrin receptor complex / receptor internalization / recycling endosome / cellular response to iron ion / 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 / Cargo recognition for clathrin-mediated endocytosis / late endosome / Platelet degranulation / virus receptor activity / positive regulation of peptidyl-serine phosphorylation / Clathrin-mediated endocytosis / positive regulation of NF-kappaB transcription factor activity / iron ion transport / cytoplasmic vesicle / antibacterial humoral response / basolateral plasma membrane / secretory granule lumen / positive regulation of canonical NF-kappaB signal transduction / intracellular iron ion homeostasis / vesicle / blood microparticle / early endosome / endosome membrane / response to hypoxia / endosome / intracellular signal transduction / apical plasma membrane / positive regulation of protein phosphorylation / external side of plasma membrane / endoplasmic reticulum lumen / intracellular membrane-bounded organelle / protein-containing complex binding / positive regulation of gene expression / negative regulation of apoptotic process / protein kinase binding / perinuclear region of cytoplasm / positive regulation of DNA-templated transcription / cell surface / protein homodimerization activity / extracellular space / RNA binding / extracellular exosome / extracellular region Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Plasmodium vivax (malaria parasite P. vivax) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Gruszczyk, J. / Huang, R.K. / Hong, C. / Yu, Z. / Tham, W.H. | |||||||||
Citation | Journal: Nature / Year: 2018 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
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6d05.cif.gz | 636.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6d05.ent.gz | 523 KB | Display | PDB format |
PDBx/mmJSON format | 6d05.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/d0/6d05 ftp://data.pdbj.org/pub/pdb/validation_reports/d0/6d05 | HTTPS FTP |
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-Related structure data
Related structure data | 7785MC 7783C 7784C 6bpaC 6bpbC 6bpcC 6bpdC 6bpeC 6d03C 6d04C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 3 types, 6 molecules ABCDEF
#1: Protein | Mass: 73940.477 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TFRC / Cell line (production host): Sf21 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P02786 #2: Protein | Mass: 77153.906 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P02787 #3: Protein | Mass: 96798.477 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Plasmodium vivax (malaria parasite P. vivax) Strain: Salvador I / Gene: PVX_094255 / Production host: Escherichia coli (E. coli) / References: UniProt: A5K736 |
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-Sugars , 2 types, 10 molecules
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #6: Sugar | ChemComp-NAG / |
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-Non-polymers , 3 types, 10 molecules
#5: Chemical | #7: Chemical | ChemComp-FE / #8: Chemical | ChemComp-CO3 / |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: ternary complex between human transferrin receptor 1, transferrin and Plasmodium vivax reticulocyte-binding protein 2b Type: COMPLEX / Details: two molecules of parasite ligand, subclass 2 / Entity ID: #1-#3 / Source: MULTIPLE SOURCES | ||||||||||||||||
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Source (natural) | Organism: homo sapiens (human) | ||||||||||||||||
Source (recombinant) | Organism: homo sapiens (human) | ||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Average exposure time: 15 sec. / Electron dose: 80 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 |
Image scans | Movie frames/image: 50 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 302858 / Symmetry type: POINT |