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- EMDB-33941: Cryo-EM structure of Coxsackievirus A16 in complex with a neutral... -
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Open data
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Basic information
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Title | Cryo-EM structure of Coxsackievirus A16 in complex with a neutralizing antibody 9B5 | |||||||||
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Function / homology | ![]() 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 / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / viral capsid ...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 / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / host cell cytoplasm / RNA helicase activity / induction by virus of host autophagy / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / DNA-templated transcription / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
![]() | Cong Y / Liu CX | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular mechanism of antibody neutralization of coxsackievirus A16. Authors: Chao Zhang / Caixuan Liu / Jinping Shi / Yalei Wang / Cong Xu / Xiaohua Ye / Qingwei Liu / Xue Li / Weihua Qiao / Yannan Yin / Yao Cong / Zhong Huang / ![]() Abstract: Coxsackievirus A16 (CVA16) causes hand, foot and mouth disease in infants and young children. However, no vaccine or anti-viral agent is currently available for CVA16. Here, the functions and working ...Coxsackievirus A16 (CVA16) causes hand, foot and mouth disease in infants and young children. However, no vaccine or anti-viral agent is currently available for CVA16. Here, the functions and working mechanisms of two CVA16-specific neutralizing monoclonal antibodies (MAbs), 9B5 and 8C4, are comprehensively investigated. Both 9B5 and 8C4 display potent neutralization in vitro and prophylactic and therapeutic efficacy in a mouse model of CVA16 infection. Mechanistically, 9B5 exerts neutralization primarily through inhibiting CVA16 attachment to cell surface via blockade of CVA16 binding to its attachment receptor, heparan sulfate, whereas 8C4 functions mainly at the post-attachment stage of CVA16 entry by interfering with the interaction between CVA16 and its uncoating receptor SCARB2. Cryo-EM studies show that 9B5 and 8C4 target distinct epitopes located at the 5-fold and 3-fold protrusions of CVA16 capsids, respectively, and exhibit differential binding preference to three forms of naturally occurring CVA16 particles. Moreover, 9B5 and 8C4 are compatible in formulating an antibody cocktail which displays the ability to prevent virus escape seen with individual MAbs. Together, our work elucidates the functional and structural basis of CVA16 antibody-mediated neutralization and protection, providing important information for design and development of effective CVA16 vaccines and antibody therapies. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 478 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.2 KB 15.2 KB | Display Display | ![]() |
Images | ![]() | 46 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7ymsMC ![]() 7y7mC ![]() 7yrfC ![]() 7yrhC ![]() 7yv2C ![]() 7yv7C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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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: 1.1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Cryo-EM structure of Coxsackievirus A16 in complex with a neutral...
Entire | Name: Cryo-EM structure of Coxsackievirus A16 in complex with a neutralizing antibody 9B5 |
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Components |
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-Supramolecule #1: Cryo-EM structure of Coxsackievirus A16 in complex with a neutral...
Supramolecule | Name: Cryo-EM structure of Coxsackievirus A16 in complex with a neutralizing antibody 9B5 type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
-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: ![]() ![]() |
Molecular weight | Theoretical: 33.080402 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GDPIADMIDQ TVNNQVNRSL TALQVLPTAA NTEASSHRLG TGVVPALQAA ETGASSNASD KNLIETRCVL NHHSTQETAI GNFFSRAGL VSIITMPTMG TQNTDGYANW DIDLMGYAQL RRKCELFTYM RFDAEFTFVV AKPNGELVPQ LLQYMYVPPG A PKPTSRDS ...String: GDPIADMIDQ TVNNQVNRSL TALQVLPTAA NTEASSHRLG TGVVPALQAA ETGASSNASD KNLIETRCVL NHHSTQETAI GNFFSRAGL VSIITMPTMG TQNTDGYANW DIDLMGYAQL RRKCELFTYM RFDAEFTFVV AKPNGELVPQ LLQYMYVPPG A PKPTSRDS FAWQTATNPS VFVKMTDPPA QVSVPFMSPA SAYQWFYDGY PTFGEHLQAN DLDYGQCPNN MMGTFSIRTV GT KKSPHSI TLRVYMRIKH VRAWIPRPLR NQPYLFKTNP NYKGNDIKCT STSRDKITTL |
-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: ![]() ![]() |
Molecular weight | Theoretical: 27.557104 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SPSAEACGYS DRVAQLTIGN STITTQEAAN IVIAYGEWPE YCPDTDATAV DKPTRPDVSV NRFFTLDTKS WAKDSKGWYW KFPDVLTEV GVFGQNAQFH YLYRSGFCVH VQCNASKFHQ GALLVAVLPE YVLGTIAGGT GNENSHPPYA TTQPGQVGAV L THPYVLDA ...String: SPSAEACGYS DRVAQLTIGN STITTQEAAN IVIAYGEWPE YCPDTDATAV DKPTRPDVSV NRFFTLDTKS WAKDSKGWYW KFPDVLTEV GVFGQNAQFH YLYRSGFCVH VQCNASKFHQ GALLVAVLPE YVLGTIAGGT GNENSHPPYA TTQPGQVGAV L THPYVLDA GIPLSQLTVC PHQWINLRTN NCATIIVPYM NTVPFDSALN HCNFGLLVIP VVPLDFNAGA TSEIPITVTI AP MCAEFAG LRQAVKQ |
-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: ![]() ![]() |
Molecular weight | Theoretical: 26.646318 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GIPTELKPGT NQFLTTDDGV SAPILPGFHP TPPIHIPGEV RNLLEICRVE TILEVNNLKT NETTPMQRLC FPVSVQSKTG ELCAAFRAD PGRDGPWQST ILGQLCRYYT QWSGSLEVTF MFAGSFMATG KMLIAYTPPG GSVPADRITA MLGTHVIWDF G LQSSVTLV ...String: GIPTELKPGT NQFLTTDDGV SAPILPGFHP TPPIHIPGEV RNLLEICRVE TILEVNNLKT NETTPMQRLC FPVSVQSKTG ELCAAFRAD PGRDGPWQST ILGQLCRYYT QWSGSLEVTF MFAGSFMATG KMLIAYTPPG GSVPADRITA MLGTHVIWDF G LQSSVTLV VPWISNTHYR AHARAGYFDY YTTGIITIWY QTNYVVPIGA PTTAYIVALA AAQDNFTMKL CKDTEDIEQT AN IQ |
-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: ![]() ![]() |
Molecular weight | Theoretical: 7.57924 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGSQVSTQRS GSHENSNSAS EGSTINYTTI NYYKDAYAAS AGRQDMSQDP KRFTDPVMDV IHEMAPPLK |
-Macromolecule #5: The heavy chain of fab 9B5
Macromolecule | Name: The heavy chain of fab 9B5 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.500203 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EVQLQQSGPE LVKPGASVKM SCKTSGYTFT ENTMHWVRQS HGKSLEWIGG IYPKNDDTKY NQKFKGKATL TVDKSSSTAC MELRSLTSE DSAVYYCARG DYENYFYAMD YWGQGTSVTV SSAKTTPPSV YPLAPGCGDT TGSSVTLGCL VKGYFPESVT V TWNSGSLS ...String: EVQLQQSGPE LVKPGASVKM SCKTSGYTFT ENTMHWVRQS HGKSLEWIGG IYPKNDDTKY NQKFKGKATL TVDKSSSTAC MELRSLTSE DSAVYYCARG DYENYFYAMD YWGQGTSVTV SSAKTTPPSV YPLAPGCGDT TGSSVTLGCL VKGYFPESVT V TWNSGSLS SSVHTFPALL QSGLYTMSSS VTVPSSTWPS QTVTCSVAHP ASSTTVDKKL |
-Macromolecule #6: The light chain of fab 9B5
Macromolecule | Name: The light chain of fab 9B5 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.600934 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DIQMTQSPAS LSVSVGETVT ITCRASENIY SNLAWYQQKQ GKSPQLLVYA ATNLADGVPS RFSGSGSGTQ YSLKINSLQS EDFGTYYCQ QFWDTPFTFG SGTKLAIKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS ...String: DIQMTQSPAS LSVSVGETVT ITCRASENIY SNLAWYQQKQ GKSPQLLVYA ATNLADGVPS RFSGSGSGTQ YSLKINSLQS EDFGTYYCQ QFWDTPFTFG SGTKLAIKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS KDSTYSMSST LTLTKDEYER HNSYTCEATH KTSTSPIVKS FNRNEC |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 38.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 3122 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |