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Open data
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Basic information
Entry | Database: PDB / ID: 6i2k | |||||||||
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Title | Structure of EV71 complexed with its receptor SCARB2 | |||||||||
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![]() | VIRUS / Enterovirus 71 / SCARB2 / Hand-foot-mouth disease / EV71 receptor | |||||||||
Function / homology | ![]() regulation of glucosylceramide catabolic process / regulation of carbohydrate catabolic process / regulation of endosome organization / aminophospholipid transport / regulation of lysosome organization / endosome to plasma membrane protein transport / protein targeting to lysosome / scavenger receptor activity / phosphatidylcholine binding / cargo receptor activity ...regulation of glucosylceramide catabolic process / regulation of carbohydrate catabolic process / regulation of endosome organization / aminophospholipid transport / regulation of lysosome organization / endosome to plasma membrane protein transport / protein targeting to lysosome / scavenger receptor activity / phosphatidylcholine binding / cargo receptor activity / cholesterol binding / phosphatidylserine binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / ribonucleoside triphosphate phosphatase activity / symbiont genome entry into host cell via pore formation in plasma membrane / lysosomal lumen / receptor-mediated endocytosis / picornain 3C / T=pseudo3 icosahedral viral capsid / clathrin-coated endocytic vesicle membrane / sensory perception of sound / host cell cytoplasmic vesicle membrane / transmembrane signaling receptor activity / positive regulation of neuron projection development / symbiont-mediated suppression of host gene expression / Cargo recognition for clathrin-mediated endocytosis / endocytic vesicle membrane / viral capsid / Clathrin-mediated endocytosis / virus receptor activity / nucleoside-triphosphate phosphatase / protein complex oligomerization / late endosome membrane / monoatomic ion channel activity / protein-folding chaperone binding / DNA replication / clathrin-dependent endocytosis of virus by host cell / host cell cytoplasm / entry receptor-mediated virion attachment to host cell / RNA helicase activity / endosome membrane / induction by virus of host autophagy / Golgi membrane / lysosomal membrane / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / focal adhesion / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / DNA-templated transcription / host cell nucleus / endoplasmic reticulum membrane / virion attachment to host cell / enzyme binding / structural molecule activity / protein homodimerization activity / proteolysis / RNA binding / extracellular exosome / ATP binding / membrane / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
![]() | Zhou, D. / Zhao, Y. / Kotecha, A. / Fry, E.E. / Kelly, J. / Wang, X. / Rao, Z. / Rowlands, D.J. / Ren, J. / Stuart, D.I. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2. Authors: Daming Zhou / Yuguang Zhao / Abhay Kotecha / Elizabeth E Fry / James T Kelly / Xiangxi Wang / Zihe Rao / David J Rowlands / Jingshan Ren / David I Stuart / ![]() ![]() ![]() Abstract: Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease-a disease endemic especially in the Asia-Pacific region. Scavenger receptor class B member 2 (SCARB2) is the major receptor of ...Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease-a disease endemic especially in the Asia-Pacific region. Scavenger receptor class B member 2 (SCARB2) is the major receptor of EV71, as well as several other enteroviruses responsible for hand, foot and mouth disease, and plays a key role in cell entry. The isolated structures of EV71 and SCARB2 are known, but how they interact to initiate infection is not. Here, we report the EV71-SCARB2 complex structure determined at 3.4 Å resolution using cryo-electron microscopy. This reveals that SCARB2 binds EV71 on the southern rim of the canyon, rather than across the canyon, as predicted. Helices 152-163 (α5) and 183-193 (α7) of SCARB2 and the viral protein 1 (VP1) GH and VP2 EF loops of EV71 dominate the interaction, suggesting an allosteric mechanism by which receptor binding might facilitate the low-pH uncoating of the virus in the endosome/lysosome. Remarkably, many residues within the binding footprint are not conserved across SCARB2-dependent enteroviruses; however, a conserved proline and glycine seem to be key residues. Thus, although the virus maintains antigenic variability even within the receptor-binding footprint, the identification of binding 'hot spots' may facilitate the design of receptor mimic therapeutics less likely to quickly generate resistance. | |||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 232 KB | Display | ![]() |
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PDB format | ![]() | 188.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 0332MC 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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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
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Components
-Protein , 5 types, 5 molecules ABCDE
#1: Protein | Mass: 32755.766 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#2: Protein | Mass: 27784.213 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#3: Protein | Mass: 26540.332 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#4: Protein | Mass: 6380.943 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#5: Protein | Mass: 47727.750 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 6 types, 8 molecules ![](data/chem/img/NAG.gif)
#6: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source | ||||||||
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#7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #9: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #10: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #12: Sugar | |
-Non-polymers , 1 types, 1 molecules ![](data/chem/img/906.gif)
#11: Chemical | ChemComp-906 / |
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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
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Source (natural) |
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Source (recombinant) | Organism: ![]() | ||||||||||||||||||||||||
Details of virus | Empty: YES / Enveloped: NO / Isolate: OTHER / Type: VIRION | ||||||||||||||||||||||||
Natural host | Organism: Homo sapiens | ||||||||||||||||||||||||
Buffer solution | pH: 5.1 | ||||||||||||||||||||||||
Specimen | Conc.: 0.6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: virus particle/SCARB2 ratio: 1:100 | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |
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Microscopy | Model: FEI POLARA 300 |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 35 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 757 |
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Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 10443 / Num. of class averages: 4 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | B value: 150 / Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||
Atomic model building |
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