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- PDB-6d05: Cryo-EM structure of a Plasmodium vivax invasion complex essentia... -
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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. | |||||||||
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![]() | CELL INVASION / malaria / Plasmodium vivax / reticulocyte / invasion | |||||||||
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 / 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 Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | Gruszczyk, J. / Huang, R.K. / Hong, C. / Yu, Z. / Tham, W.H. | |||||||||
![]() | ![]() 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 | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 636.7 KB | Display | ![]() |
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PDB format | ![]() | 523 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 92 KB | Display | |
Data in CIF | ![]() | 141 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-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 ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() ![]() #2: Protein | Mass: 77153.906 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #3: Protein | Mass: 96798.477 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Strain: Salvador I / Gene: PVX_094255 / Production host: ![]() ![]() |
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-Sugars , 2 types, 10 molecules ![](data/chem/img/NAG.gif)
#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 ![](data/chem/img/CA.gif)
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#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 |
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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: ![]() | ||||||||||||||||
Source (recombinant) | Organism: ![]() | ||||||||||||||||
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 |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
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 |
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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 |