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Yorodumi- EMDB-68830: CryoEM structure of EV-D68 US/MO/14-18947 in complex with MFSD6-L3 -
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Basic information
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| Title | CryoEM structure of EV-D68 US/MO/14-18947 in complex with MFSD6-L3 | |||||||||
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Keywords | EV-D68 / MFSD6 / VIRUS | |||||||||
| Function / homology | Function and homology informationsymbiont-mediated suppression of cytoplasmic pattern recognition receptor signaling pathway / antigen processing and presentation of exogenous peptide antigen via MHC class I / host cell mitochondrion / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / 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 / protein sequestering activity ...symbiont-mediated suppression of cytoplasmic pattern recognition receptor signaling pathway / antigen processing and presentation of exogenous peptide antigen via MHC class I / host cell mitochondrion / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / 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 / protein sequestering activity / host cell cytoplasmic vesicle membrane / ribonucleoside triphosphate phosphatase activity / nucleoside-triphosphate phosphatase / channel activity / monoatomic ion transmembrane transport / symbiont-mediated suppression of host toll-like receptor signaling pathway / symbiont-mediated suppression of host NF-kappaB cascade / RNA helicase activity / symbiont-mediated suppression of host innate immune response / endocytosis involved in viral entry into host cell / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / virion attachment to host cell / host cell nucleus / structural molecule activity / proteolysis / DNA-templated transcription / RNA binding / zinc ion binding / ATP binding / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||
| Biological species | enterovirus D68 / Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.47 Å | |||||||||
Authors | Liang SJ / Lou ZY | |||||||||
| Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2026Title: A dual-receptor checkpoint primes enterovirus D68 for respiratory cell entry. Authors: Shengjian Liang / Haoran Guo / Zhili Xu / Zan Liu / Wanying Yang / Xiaoke Liu / Zhenyu Wei / Jichao Hou / Wei Huang / Wei Wang / Jiachen Li / Wendong Ma / Zhikang Deng / Haocong Qian / Yaxin ...Authors: Shengjian Liang / Haoran Guo / Zhili Xu / Zan Liu / Wanying Yang / Xiaoke Liu / Zhenyu Wei / Jichao Hou / Wei Huang / Wei Wang / Jiachen Li / Wendong Ma / Zhikang Deng / Haocong Qian / Yaxin Wang / Jialin Liu / Zihe Rao / Wei Wei / Zhiyong Lou / ![]() Abstract: MFSD6 is a newly identified receptor that mediates the invasion of respiratory cells by enterovirus D68 (EV-D68), a non-polio enterovirus that causes severe respiratory disease and poliomyelitis-like ...MFSD6 is a newly identified receptor that mediates the invasion of respiratory cells by enterovirus D68 (EV-D68), a non-polio enterovirus that causes severe respiratory disease and poliomyelitis-like illness in children. Here, we report near-atomic-resolution cryo-electron microscopy (cryo-EM) structures of historical and contemporary AFM-associated EV-D68 strains, together with their complexes bound to the third extracellular loop of MFSD6 (MFSD6-L3). These structures uncover a previously unrecognized "binary gating switch" mechanism of virus-receptor engagement that differs from the reported model. In this mechanism, the N200-V208 segment of MFSD6, carrying a glycosylated Asn207, inserts into one capsomer, whereas the sialyl-Gal-terminated glycan of MFSD6 engages an adjacent capsomer. Neu5Ac binding induces conformational rearrangements that expel the pocket factor, destabilize the virion, and prime infection. Functional analyses further define the contributions of the receptor-contacting residues and glycans to viral attachment and entry. Together, our findings refine the molecular basis of EV-D68 recognition of MFSD6 and reveal a glycan-mediated dual-lock mechanism that may enhance receptor specificity, prevent premature uncoating, and ensure productive infection only upon engagement of the correct host receptor. These results provide broader insight into enterovirus tropism and establish a framework for structure-guided antiviral design. | |||||||||
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Structure visualization
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_68830.map.gz | 20.9 MB | EMDB map data format | |
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| Header (meta data) | emd-68830-v30.xml emd-68830.xml | 19.8 KB 19.8 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_68830_fsc.xml | 7.4 KB | Display | FSC data file |
| Images | emd_68830.png | 147.8 KB | ||
| Filedesc metadata | emd-68830.cif.gz | 6.6 KB | ||
| Others | emd_68830_half_map_1.map.gz emd_68830_half_map_2.map.gz | 39.7 MB 39.7 MB | ||
| Archive directory | https://data.pdbj.org/pub/emdb/structures/EMD-68830 ftp://data.pdbj.org/pub/emdb/structures/EMD-68830 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 23bgMC ![]() 23ayC ![]() 23bxC ![]() 23psC ![]() 9vv0C ![]() 9w0dC ![]() 9w0eC ![]() 9w0iC ![]() 9w0jC ![]() 9w0kC ![]() 9w34C ![]() 9w4oC ![]() 9w4yC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_68830.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.931 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #1
| File | emd_68830_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #2
| File | emd_68830_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : enterovirus D68
| Entire | Name: enterovirus D68 |
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| Components |
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-Supramolecule #1: enterovirus D68
| Supramolecule | Name: enterovirus D68 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 42789 / Sci species name: enterovirus D68 / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: No / Virus empty: No |
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-Macromolecule #1: Capsid protein VP1
| Macromolecule | Name: Capsid protein VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A |
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| Source (natural) | Organism: enterovirus D68 |
| Molecular weight | Theoretical: 32.819207 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: IESIIKTATD TVKSEINAEL GVVPSLNAVE TGATSNTEPE EAIQTRTVIN QHGVSETLVE NFLSRAALVS KRSFEYKDHT SSTARADKN FFKWTINTRS FVQLRRKLEL FTYLRFDAEI TILTTVAVNG SGNNTYVGLP DLTLQAMFVP TGALTPEKQD S FHWQSGSN ...String: IESIIKTATD TVKSEINAEL GVVPSLNAVE TGATSNTEPE EAIQTRTVIN QHGVSETLVE NFLSRAALVS KRSFEYKDHT SSTARADKN FFKWTINTRS FVQLRRKLEL FTYLRFDAEI TILTTVAVNG SGNNTYVGLP DLTLQAMFVP TGALTPEKQD S FHWQSGSN ASVFFKISDP PARITIPFMC INSAYSVFYD GFAGFEKNGL YGINPADTIG NLCVRIVNEH QPVGFTVTVR VY MKPKHIK AWAPRPPRTL PYMSIANANY KGKERAPNAL SAIIGNRDSV KTMPHNIVN UniProtKB: Genome polyprotein |
-Macromolecule #2: Capsid protein VP2
| Macromolecule | Name: Capsid protein VP2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A |
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| Source (natural) | Organism: enterovirus D68 |
| Molecular weight | Theoretical: 26.573094 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: SDRVLQLKLG NSAIVTQEAA NYCCAYGEWP NYLPDHEAVA IDKPTQPETA TDRFYTLKSV KWETGSTGWW WKLPDALNNI GMFGQNVQH HYLYRSGFLI HVQCNATKFH QGALLVVAIP EHQRGAHNTN TSPGFDDIMK GEEGGTFNHP YVLDDGTSLA C ATIFPHQW ...String: SDRVLQLKLG NSAIVTQEAA NYCCAYGEWP NYLPDHEAVA IDKPTQPETA TDRFYTLKSV KWETGSTGWW WKLPDALNNI GMFGQNVQH HYLYRSGFLI HVQCNATKFH QGALLVVAIP EHQRGAHNTN TSPGFDDIMK GEEGGTFNHP YVLDDGTSLA C ATIFPHQW INLRTNNSAT IVLPWMNAAP MDFPLRHNQW TLAIIPVVPL GTRTTSSMVP ITVSIAPMCC EFNGLRHAIT UniProtKB: Genome polyprotein |
-Macromolecule #3: Capsid protein VP3
| Macromolecule | Name: Capsid protein VP3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A |
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| Source (natural) | Organism: enterovirus D68 |
| Molecular weight | Theoretical: 27.112814 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: GVPTYLLPGS GQFLTTDDHS SAPALPCFNP TPEMHIPGQV RNMLEVVQVE SMMEINNTES AVGMERLKVD ISALTDVDQL LFNIPLDIQ LDGPLRNTLV GNISRYYTHW SGSLEMTFMF CGSFMAAGKL ILCYTPPGGS CPTTRETAML GTHIVWDFGL Q SSVTLIIP ...String: GVPTYLLPGS GQFLTTDDHS SAPALPCFNP TPEMHIPGQV RNMLEVVQVE SMMEINNTES AVGMERLKVD ISALTDVDQL LFNIPLDIQ LDGPLRNTLV GNISRYYTHW SGSLEMTFMF CGSFMAAGKL ILCYTPPGGS CPTTRETAML GTHIVWDFGL Q SSVTLIIP WISGSHYRMF NNDAKSTNAN VGYVTCFMQT NLIVPSESSD TCSLIGFIAA KDDFSLRLMR DSPDIGQLDH LH AAEAAYQ UniProtKB: Genome polyprotein |
-Macromolecule #4: Capsid protein VP4
| Macromolecule | Name: Capsid protein VP4 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: enterovirus D68 |
| Molecular weight | Theoretical: 4.210649 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: INFYKDSYAA SASKQDFSQD PSKFTEPVVE GLKAGAPVL UniProtKB: Genome polyprotein |
-Macromolecule #5: Major facilitator superfamily domain-containing protein 6
| Macromolecule | Name: Major facilitator superfamily domain-containing protein 6 type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 14.623599 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: KPATLRCVPK IRPTTHPTNA SHQLTILPTN SSFTSFLTIS PKMREKRNLL ETRLNVSDTV TLPTAPNMNS EPTLQPQTGE ITNRMMDLT LNSSTATPVS PGSVTKETTT VIVTTTKSLP SDQVMLVYDQ QEVE UniProtKB: Major facilitator superfamily domain-containing protein 6 |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 50.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi



enterovirus D68
Keywords
Homo sapiens (human)
Authors
China, 1 items
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Processing
FIELD EMISSION GUN

