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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-0332 | |||||||||
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Title | Structure of EV71 complexed with its receptor SCARB2 | |||||||||
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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 | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
![]() | Zhou D / Zhao Y / Kotecha A / Fry EE / Kelly J / Wang X / Rao Z / Rowlands DJ / Ren J / Stuart DI | |||||||||
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 | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 229.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.4 KB 17.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.9 KB | Display | ![]() |
Images | ![]() | 298.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6i2kMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
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Related items in Molecule of the Month |
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Map
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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 : complex of EV71 and SCARB2
+Supramolecule #1: complex of EV71 and SCARB2
+Supramolecule #3: SCARB2
+Supramolecule #2: Enterovirus A71
+Macromolecule #1: Polyprotein
+Macromolecule #2: Polyprotein
+Macromolecule #3: Polyprotein
+Macromolecule #4: Polyprotein
+Macromolecule #5: Lysosome membrane protein 2
+Macromolecule #11: 1-(2-aminopyridin-4-yl)-3-[(3S)-5-{4-[(E)-(ethoxyimino)methyl]phe...
+Macromolecule #12: 2-acetamido-2-deoxy-beta-D-glucopyranose
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.6 mg/mL |
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Buffer | pH: 5.1 |
Vitrification | Cryogen name: ETHANE |
Details | virus particle/SCARB2 ratio: 1:100 |
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Electron microscopy
Microscope | FEI POLARA 300 |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Number real images: 757 / Average electron dose: 35.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |