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Yorodumi- PDB-6d04: Cryo-EM structure of a Plasmodium vivax invasion complex essentia... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6d04 | |||||||||
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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 1. | |||||||||
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 / 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 Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Plasmodium vivax (malaria parasite P. vivax) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.74 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 | 6d04.cif.gz | 637 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6d04.ent.gz | 523.1 KB | Display | PDB format |
PDBx/mmJSON format | 6d04.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6d04_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 6d04_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 6d04_validation.xml.gz | 90.9 KB | Display | |
Data in CIF | 6d04_validation.cif.gz | 140 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/d0/6d04 ftp://data.pdbj.org/pub/pdb/validation_reports/d0/6d04 | HTTPS FTP |
-Related structure data
Related structure data | 7784MC 7783C 7785C 6bpaC 6bpbC 6bpcC 6bpdC 6bpeC 6d03C 6d05C 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 1 / 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 FIELD |
Image recording | Average exposure time: 15 sec. / Electron dose: 80 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 |
Image scans | Sampling size: 5 µm / Movie frames/image: 50 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
3D reconstruction | Resolution: 3.74 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 287253 / Symmetry type: POINT |