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- EMDB-65038: Structure of mature CVA6 virus complexed with 1F4 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-65038
TitleStructure of mature CVA6 virus complexed with 1F4 Fab
Map data
Sample
  • Complex: mature CVA6 virus complexed with 1F4 Fab
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: VH
    • Protein or peptide: VL
  • Ligand: STEARIC ACID
Keywordscoxsackievirus A6 / KRM1 / receptor / VIRUS
Function / homology
Function and homology information


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 / host cell cytoplasmic vesicle membrane / virion component / viral capsid / ribonucleoside triphosphate phosphatase activity ...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 / host cell cytoplasmic vesicle membrane / virion component / viral capsid / ribonucleoside triphosphate phosphatase activity / host cell / nucleoside-triphosphate phosphatase / channel activity / monoatomic ion transmembrane transport / DNA replication / RNA helicase activity / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / symbiont entry into host cell / DNA-templated transcription / virion attachment to host cell / host cell nucleus / structural molecule activity / proteolysis / RNA binding / zinc ion binding / ATP binding
Similarity search - Function
Protein of unknown function DUF3724, picornavirus / Protein of unknown function (DUF3724) / Picornavirus coat protein VP4 superfamily / : / Picornavirus coat protein / Poliovirus 3A protein-like / Poliovirus 3A protein like / Picornavirus 2B protein / Poliovirus core protein 3a, soluble domain / Picornavirus 2B protein ...Protein of unknown function DUF3724, picornavirus / Protein of unknown function (DUF3724) / Picornavirus coat protein VP4 superfamily / : / Picornavirus coat protein / Poliovirus 3A protein-like / Poliovirus 3A protein like / Picornavirus 2B protein / Poliovirus core protein 3a, soluble domain / Picornavirus 2B protein / Peptidase C3, picornavirus core protein 2A / Picornavirus core protein 2A / Picornavirus coat protein VP4 / Picornavirus coat protein (VP4) / Peptidase C3A/C3B, picornaviral / 3C cysteine protease (picornain 3C) / Picornavirales 3C/3C-like protease domain / Picornavirales 3C/3C-like protease domain profile. / Picornavirus capsid / picornavirus capsid protein / Helicase, superfamily 3, single-stranded RNA virus / Superfamily 3 helicase of positive ssRNA viruses domain profile. / Helicase, superfamily 3, single-stranded DNA/RNA virus / RNA helicase / Picornavirus/Calicivirus coat protein / Viral coat protein subunit / Reverse transcriptase/Diguanylate cyclase domain / RNA-directed RNA polymerase, C-terminal domain / Viral RNA-dependent RNA polymerase / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Genome polyprotein / Genome polyprotein / Genome polyprotein / Genome polyprotein
Similarity search - Component
Biological speciesHomo sapiens (human) / Coxsackievirus A6 / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.11 Å
AuthorsKe X / Li X / Liu Z / Liu K / Yan X / Shu B / Zhang C
Funding support China, 1 items
OrganizationGrant numberCountry
National Science Foundation (NSF, China) China
CitationJournal: Nat Commun / Year: 2025
Title: Molecular mechanisms of receptor recognition and antibody neutralization of coxsackievirus A6.
Authors: Xianliang Ke / Xue Li / Zeyu Liu / Kexin Liu / Weichi Liu / Xingyu Yan / Bo Shu / Chao Zhang /
Abstract: Coxsackievirus A6 (CVA6), a major cause of hand, foot, and mouth disease, lacks approved vaccines or drugs. KRM1 is its only known receptor, but its precise role remains unclear. This study ...Coxsackievirus A6 (CVA6), a major cause of hand, foot, and mouth disease, lacks approved vaccines or drugs. KRM1 is its only known receptor, but its precise role remains unclear. This study investigates CVA6's entry mechanism and antibody neutralization. Cryo-EM shows CVA6 clinical strain HeB primarily exists as mature virions. KRM1 binding within the canyon triggers conversion to uncoating intermediate, defining KRM1 as an uncoating receptor for CVA6. However, KRM1 knockout reduces CVA6 infectivity without affecting attachment. Conversely, disrupting heparan sulfate proteoglycan (HSPG) impairs both viral attachment and infectivity, and CVA6 virions bind heparin directly. These results support a two-receptor entry model for CVA6: HSPG mediates viral attachment, while KRM1 induces uncoating. Additionally, we develop two CVA6-specific protective antibodies (1F4 and 3H7), targeting a new antigenic site near the three-fold axis of the viral capsid. These antibodies sterically block KRM1 binding and function post-attachment, consistent with KRM1's role. The findings elucidate CVA6 entry and offer a basis for antibody interventions.
History
DepositionJun 11, 2025-
Header (metadata) releaseNov 19, 2025-
Map releaseNov 19, 2025-
UpdateJun 10, 2026-
Current statusJun 10, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_65038.png

Downloads & links

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Map

FileDownload / File: emd_65038.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.95 Å/pix.
x 600 pix.
= 570. Å		0.95 Å/pix.
x 600 pix.
= 570. Å		0.95 Å/pix.
x 600 pix.
= 570. Å

Surface

Projections

Slices (1/3)

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.95 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.05
Minimum - Maximum-0.24918287 - 0.71202445
Average (Standard dev.)0.003534216 (±0.041842103)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions600600600
Spacing600600600
CellA=B=C: 570.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_65038_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_65038_half_map_2.map
Projections & Slices
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Histogram

Histogram (log scale)

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Sample components

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Entire : mature CVA6 virus complexed with 1F4 Fab

EntireName: mature CVA6 virus complexed with 1F4 Fab
Components
  • Complex: mature CVA6 virus complexed with 1F4 Fab
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: VH
    • Protein or peptide: VL
  • Ligand: STEARIC ACID

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Supramolecule #1: mature CVA6 virus complexed with 1F4 Fab

SupramoleculeName: mature CVA6 virus complexed with 1F4 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Details: Purified Coxsackievirus A6 (CV-A6) virions were combined with 1F4 Fab at a 1:120 molar ratio (virus:protein) in PBS (pH 7.4). The binding reaction was carried out at room temperature for 30 ...Details: Purified Coxsackievirus A6 (CV-A6) virions were combined with 1F4 Fab at a 1:120 molar ratio (virus:protein) in PBS (pH 7.4). The binding reaction was carried out at room temperature for 30 minutes to allow complex formation. Immediately following incubation, samples were rapidly vitrified for cryo-EM analysis by plunge-freezing in liquid ethane.
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Genome polyprotein

MacromoleculeName: Genome polyprotein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Coxsackievirus A6
Molecular weightTheoretical: 33.568379 KDa
SequenceString: NDPITNAVES AVSALADTTI SRVTAANTAA STHSLGTGRV PALQAAETGA SSNSSDENLI ETRCVMNRNG VNEASVEHFY SRAGLVGVV EVKDSGTSLD GYTVWPIDVM GFVQQRRKLE LSTYMRFDAE FTFVSNLNNS TTPGMLLQYM YVPPGAPKPD S RKSYQWQT ...String:
NDPITNAVES AVSALADTTI SRVTAANTAA STHSLGTGRV PALQAAETGA SSNSSDENLI ETRCVMNRNG VNEASVEHFY SRAGLVGVV EVKDSGTSLD GYTVWPIDVM GFVQQRRKLE LSTYMRFDAE FTFVSNLNNS TTPGMLLQYM YVPPGAPKPD S RKSYQWQT ATNPSVFAKL SDPPPQVSVP FMSPATAYQW FYDGYPTFGE HKQATNLQYG QCPNNMMGHF AIRTVSESTT GK NIHVRVY MRIKHVRAWV PRPLRSQAYM VKNYPTYSQT ITNTATDRAS ITTTDYEGGV PASPQRTS

UniProtKB: Genome polyprotein

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Macromolecule #2: Genome polyprotein

MacromoleculeName: Genome polyprotein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A
Source (natural)Organism: Coxsackievirus A6
Molecular weightTheoretical: 28.138604 KDa
SequenceString: SPSVEACGYS DRVAQLTVGN STITTQEAAN IVLSYGEWPE YCPSTDATAV DKPTRPDVSV NRFYTLSTKS WKTESTGWYW KFPDVLNDT GVFGQNAQFH YLYRSGFCMH VQCNASKFHQ GALLVAAIPE FVIAASSPAT KPNSQGLYPD FAHTNPGKDG Q EFRDPYVL ...String:
SPSVEACGYS DRVAQLTVGN STITTQEAAN IVLSYGEWPE YCPSTDATAV DKPTRPDVSV NRFYTLSTKS WKTESTGWYW KFPDVLNDT GVFGQNAQFH YLYRSGFCMH VQCNASKFHQ GALLVAAIPE FVIAASSPAT KPNSQGLYPD FAHTNPGKDG Q EFRDPYVL DAGIPLSQAL IFPHQWINLR TNNCATIIMP YINALPFDSA LNHSNFGLVV IPISPLKYCN GATTEVPITL TI APLNSEF SGLRQAIKQ

UniProtKB: Genome polyprotein

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Macromolecule #3: Genome polyprotein

MacromoleculeName: Genome polyprotein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A
Source (natural)Organism: Coxsackievirus A6
Molecular weightTheoretical: 26.32476 KDa
SequenceString: GFPTELKPGT NQFLTTDDGT SPPILPGFEP TPLIHIPGEF TSLLDLCQVE TILEVNNTTG TTGVSRLLIP VRAQNNVDQL CASFQVDPG RNGPWQSTMV GQICRYYTQW SGSLKVTFMF TGSFMATGKM LIAYTPPGSA QPTTREAAML GTHIVWDFGL Q SSVTLVIP ...String:
GFPTELKPGT NQFLTTDDGT SPPILPGFEP TPLIHIPGEF TSLLDLCQVE TILEVNNTTG TTGVSRLLIP VRAQNNVDQL CASFQVDPG RNGPWQSTMV GQICRYYTQW SGSLKVTFMF TGSFMATGKM LIAYTPPGSA QPTTREAAML GTHIVWDFGL Q SSVTLVIP WISNTHFRAV KTGGVYDYYA TGIVTIWYQT NFVVPPDTPT EANIIALGAA QKNFTLKLCK DTDEIQQTAE YQ

UniProtKB: Genome polyprotein

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Macromolecule #4: Genome polyprotein

MacromoleculeName: Genome polyprotein / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Coxsackievirus A6
Molecular weightTheoretical: 7.503163 KDa
SequenceString:
MGAQVSTQKS GSHETRNVAT EGSTINFTNI NYYKDSYAAS ASRQDFAQDP AKFTRPVLDA IREAAAPLQ

UniProtKB: Genome polyprotein

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Macromolecule #5: VH

MacromoleculeName: VH / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 12.667063 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
SequenceString:
QVQLQQSGAE LVKPGASVKL SCKASGYTFT SYYMYWVKQR PGQGLEWIGE INPSNGGTNF NEKFKSKATL TVDKSSSTAY MQLSSLTSE DSAVYYCTRY GNYAYWGQGT LVTVSA

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Macromolecule #6: VL

MacromoleculeName: VL / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 11.676889 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
SequenceString:
DIQMTQSPAS LSVSVGETVT ITCRASENIY SNLAWYQQKQ GKSPQLLVYA ATNLADGVPS RFSGSGSGTQ YSLKINSLQS EDFGSYYCQ HFWGTPWTFG GGTKLEIK

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Macromolecule #7: STEARIC ACID

MacromoleculeName: STEARIC ACID / type: ligand / ID: 7 / Number of copies: 1 / Formula: STE
Molecular weightTheoretical: 284.477 Da
Chemical component information

ChemComp-STE:
STEARIC ACID

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
GridModel: EMS Lacey Carbon / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: LACEY
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 273.0 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeJEOL CRYO ARM 300
Image recordingFilm or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Number real images: 4570 / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm
Sample stageSpecimen holder model: JEOL CRYOSPECPORTER / Cooling holder cryogen: NITROGEN

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Image processing

Particle selectionNumber selected: 153424
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
In silico model: AB-initio reconstructuction in cryoSPARC (V4.5.3)
Final reconstructionApplied symmetry - Point group: I (icosahedral) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 2.11 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 81877
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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