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Open data
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Basic information
Entry | Database: PDB / ID: 6cv3 | ||||||
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Title | CryoEM structure of human enterovirus D68 emptied particle | ||||||
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![]() | VIRUS / genome release / receptor | ||||||
Function / homology | ![]() picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / nucleoside-triphosphate phosphatase / protein complex oligomerization ...picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / RNA helicase activity / symbiont-mediated suppression of host innate immune response / symbiont entry into host cell / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / host cell nucleus / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.56 Å | ||||||
![]() | Liu, Y. / Rossmann, M.G. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Bypassing pan-enterovirus host factor PLA2G16. Authors: Jim Baggen / Yue Liu / Heyrhyoung Lyoo / Arno L W van Vliet / Maryam Wahedi / Jost W de Bruin / Richard W Roberts / Pieter Overduin / Adam Meijer / Michael G Rossmann / Hendrik Jan Thibaut / ...Authors: Jim Baggen / Yue Liu / Heyrhyoung Lyoo / Arno L W van Vliet / Maryam Wahedi / Jost W de Bruin / Richard W Roberts / Pieter Overduin / Adam Meijer / Michael G Rossmann / Hendrik Jan Thibaut / Frank J M van Kuppeveld / ![]() ![]() Abstract: Enteroviruses are a major cause of human disease. Adipose-specific phospholipase A2 (PLA2G16) was recently identified as a pan-enterovirus host factor and potential drug target. In this study, we ...Enteroviruses are a major cause of human disease. Adipose-specific phospholipase A2 (PLA2G16) was recently identified as a pan-enterovirus host factor and potential drug target. In this study, we identify a possible mechanism of PLA2G16 evasion by employing a dual glycan receptor-binding enterovirus D68 (EV-D68) strain. We previously showed that this strain does not strictly require the canonical EV-D68 receptor sialic acid. Here, we employ a haploid screen to identify sulfated glycosaminoglycans (sGAGs) as its second glycan receptor. Remarkably, engagement of sGAGs enables this virus to bypass PLA2G16. Using cryo-EM analysis, we reveal that, in contrast to sialic acid, sGAGs stimulate genome release from virions via structural changes that enlarge the putative openings for genome egress. Together, we describe an enterovirus that can bypass PLA2G16 and identify additional virion destabilization as a potential mechanism to circumvent PLA2G16. | ||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 148.1 KB | Display | ![]() |
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PDB format | ![]() | 114 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7634MC ![]() 7632C ![]() 7633C ![]() 7635C ![]() 7636C ![]() 7638C ![]() 6cv1C ![]() 6cv2C ![]() 6cv4C ![]() 6cv5C ![]() 6cvbC 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
#1: Protein | Mass: 32957.449 Da / Num. of mol.: 1 / Fragment: UNP residues 565-861 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#2: Protein | Mass: 27170.895 Da / Num. of mol.: 1 / Fragment: UNP residues 1-247 / Source method: isolated from a natural source / Source: (natural) ![]() |
#3: Protein | Mass: 27595.215 Da / Num. of mol.: 1 / Fragment: UNP residues 1-248 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY / Number of used crystals: 1 |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Enterovirus D68 / Type: VIRUS / Entity ID: all / Source: NATURAL |
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Source (natural) | Organism: ![]() |
Details of virus | Empty: YES / Enveloped: NO / Isolate: STRAIN / Type: VIRION |
Natural host | Organism: Homo sapiens |
Buffer solution | pH: 7.2 / Details: phosphate buffer |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Homemade |
Vitrification | Instrument: GATAN CRYOPLUNGE 3 / Cryogen name: ETHANE / Humidity: 85 % / Chamber temperature: 298 K |
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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 / Nominal magnification: 22500 X / Calibrated defocus min: 500 nm / Calibrated defocus max: 3100 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 7 sec. / Electron dose: 33 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 218 |
Image scans | Sampling size: 5 µm / Width: 3838 / Height: 3710 / Movie frames/image: 28 / Used frames/image: 2-28 |
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Processing
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EM software |
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CTF correction | Details: On-the-fly CTF correction during 2D alignment and 3D reconstruction Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 9870 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.56 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 2107 / Algorithm: FOURIER SPACE / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL / Target criteria: correlation coefficient | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 483.36 Å2 / Biso mean: 84.0183 Å2 / Biso min: 2 Å2 |