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- EMDB-60997: VLP structure of Chikungunya virus complexed with C34 Fab, 2f block. -

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Basic information

Entry
Database: EMDB / ID: EMD-60997
TitleVLP structure of Chikungunya virus complexed with C34 Fab, 2f block.
Map data
Sample
  • Complex: CHIKV VLP
    • Protein or peptide: C34 Fab, Heavy Chain
    • Protein or peptide: C34 Fab, Light Chain
    • Protein or peptide: CHIKV E1
    • Protein or peptide: Structural polyprotein
    • Protein or peptide: CHIKV capsid protein
  • Ligand: CHOLESTEROL
Keywordschikungunya / alphavirus / VIRUS LIKE PARTICLE / antibody
Function / homology
Function and homology information


T=4 icosahedral viral capsid / host cell cytoplasm / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / symbiont entry into host cell / virion attachment to host cell / host cell nucleus / host cell plasma membrane / virion membrane / structural molecule activity ...T=4 icosahedral viral capsid / host cell cytoplasm / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / symbiont entry into host cell / virion attachment to host cell / host cell nucleus / host cell plasma membrane / virion membrane / structural molecule activity / proteolysis / RNA binding / membrane
Similarity search - Function
Alphavirus E2 glycoprotein, domain B / Peptidase S3, togavirin / Alphavirus E2 glycoprotein / Alphavirus E3 spike glycoprotein / Alphavirus E1 glycoprotein / Alphavirus E2 glycoprotein, domain A / Alphavirus E2 glycoprotein, domain C / Alphavirus E2 glycoprotein / Alphavirus core protein / Alphavirus E3 glycoprotein ...Alphavirus E2 glycoprotein, domain B / Peptidase S3, togavirin / Alphavirus E2 glycoprotein / Alphavirus E3 spike glycoprotein / Alphavirus E1 glycoprotein / Alphavirus E2 glycoprotein, domain A / Alphavirus E2 glycoprotein, domain C / Alphavirus E2 glycoprotein / Alphavirus core protein / Alphavirus E3 glycoprotein / Alphavirus E1 glycoprotein / Alphavirus core protein (CP) domain profile. / Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily / Flavivirus glycoprotein, central and dimerisation domain superfamily / Flaviviral glycoprotein E, dimerisation domain / Immunoglobulin E-set / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan
Similarity search - Domain/homology
Structural polyprotein / Structural polyprotein / Structural polyprotein
Similarity search - Component
Biological speciesChikungunya virus / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.73 Å
AuthorsHan X / Ji C / Wang F / Tian S / Gao FG / Yan J
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Nat Commun / Year: 2025
Title: Neutralizing antibodies against Chikungunya virus and structural elucidation of their mechanism of action.
Authors: Xiaonan Han / Chengfan Ji / Siyu Tian / Fengze Wang / Guo-Ping Cao / Ding Li / Xiaomin Duan / Zhou Tong / Jianxun Qi / Qihui Wang / Qingrui Huang / Bing-Dong Zhan / George Fu Gao / Jinghua Yan /
Abstract: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes febrile illness and acute or chronic arthritis. Most therapeutics are still in the pre-clinical stage. In this study, we report ...Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes febrile illness and acute or chronic arthritis. Most therapeutics are still in the pre-clinical stage. In this study, we report the isolation of two neutralizing antibodies, C34 and C37, from a convalescent patient and investigate their mechanisms of action. Both C34 and C37 exhibit high neutralizing activities in vitro and demonstrate protective effects against CHIKV in a female mouse model. Our functional and structural studies reveal a mechanism that inhibits multiple stages of the virus infection cycle. Both antibodies bind with high affinity to an epitope spanning E2, E1, and the connecting β-strands, facilitating intra- and inter-virion crosslinking. Cryo-EM structures additionally identify a minor patch located beneath the E3 binding site on E2, which is allosterically exposed upon E3 dissociation during virus maturation. Functional and structural data further suggest that binding to the CHIKV receptor, Mxra8, is obstructed due to a clash between the antibodies and the stalk region of Mxra8. Our results highlight the potential of antibody-based therapeutics against CHIKV and elucidate the mechanisms of monoclonal antibody protection.
History
DepositionJul 30, 2024-
Header (metadata) releaseNov 12, 2025-
Map releaseNov 12, 2025-
UpdateNov 12, 2025-
Current statusNov 12, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_60997.map.gz / Format: CCP4 / Size: 190.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.34 Å/pix.
x 368 pix.
= 493.12 Å
1.34 Å/pix.
x 368 pix.
= 493.12 Å
1.34 Å/pix.
x 368 pix.
= 493.12 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.34 Å
Density
Contour LevelBy AUTHOR: 0.135
Minimum - Maximum-0.59633464 - 0.94410944
Average (Standard dev.)0.0047084005 (±0.042171896)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions368368368
Spacing368368368
CellA=B=C: 493.12003 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_60997_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_60997_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : CHIKV VLP

EntireName: CHIKV VLP
Components
  • Complex: CHIKV VLP
    • Protein or peptide: C34 Fab, Heavy Chain
    • Protein or peptide: C34 Fab, Light Chain
    • Protein or peptide: CHIKV E1
    • Protein or peptide: Structural polyprotein
    • Protein or peptide: CHIKV capsid protein
  • Ligand: CHOLESTEROL

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Supramolecule #1: CHIKV VLP

SupramoleculeName: CHIKV VLP / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Chikungunya virus

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Macromolecule #1: C34 Fab, Heavy Chain

MacromoleculeName: C34 Fab, Heavy Chain / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 28.360697 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: METDTLLLWV LLLWVPGSTG DEVQLVESGG GLVQPGRSLR LSCAASGFTF DDYAMHWVRQ APGKGLEWVS GISWNSGSIG YADSVKGRF TISRDNAKNS LYLQMNSLRA EDTALYYCAK DMGYSGNDDY YGMDVWGQGT TVTVSSASTK GPSVFPLAPS S KSTSGGTA ...String:
METDTLLLWV LLLWVPGSTG DEVQLVESGG GLVQPGRSLR LSCAASGFTF DDYAMHWVRQ APGKGLEWVS GISWNSGSIG YADSVKGRF TISRDNAKNS LYLQMNSLRA EDTALYYCAK DMGYSGNDDY YGMDVWGQGT TVTVSSASTK GPSVFPLAPS S KSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VD KRVEPKS CDKTHTCPPC PHHHHHH

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Macromolecule #2: C34 Fab, Light Chain

MacromoleculeName: C34 Fab, Light Chain / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 26.472525 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ELATMETDTL LLWVLLLWVP GSTGDDIQLT QSPSSLSASV GDRVTITCRA SQRISSYLNW YQQKPGKAPK LLIYGAFSLQ SGVPSRFSG SGSGTDFTLT ISSLQPEDFA TYYCQQSYRT LTRTFGQGTK VEIKRTVAAP SVFIFPPSDE QLKSGTASVV C LLNNFYPR ...String:
ELATMETDTL LLWVLLLWVP GSTGDDIQLT QSPSSLSASV GDRVTITCRA SQRISSYLNW YQQKPGKAPK LLIYGAFSLQ SGVPSRFSG SGSGTDFTLT ISSLQPEDFA TYYCQQSYRT LTRTFGQGTK VEIKRTVAAP SVFIFPPSDE QLKSGTASVV C LLNNFYPR EAKVQWKVDN ALQSGNSQES VTEQDSKDST YSLSSTLTLS KADYEKHKVY ACEVTHQGLS SPVTKSFNRG EC S

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Macromolecule #3: CHIKV E1

MacromoleculeName: CHIKV E1 / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Chikungunya virus
Molecular weightTheoretical: 47.446906 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: YEHVTVIPNT VGVPYKTLVN RPGYSPMVLE MELLSVTLEP TLSLDYITCE YKTVIPSPYV KCCGTAECKD KNLPDYSCKV FTGVYPFMW GGAYCFCDAE NTQLSEAHVE KSESCKTEFA SAYRAHTASA SAKLRVLYQG NNITVTAYAN GDHAVTVKDA K FIVGPMSS ...String:
YEHVTVIPNT VGVPYKTLVN RPGYSPMVLE MELLSVTLEP TLSLDYITCE YKTVIPSPYV KCCGTAECKD KNLPDYSCKV FTGVYPFMW GGAYCFCDAE NTQLSEAHVE KSESCKTEFA SAYRAHTASA SAKLRVLYQG NNITVTAYAN GDHAVTVKDA K FIVGPMSS AWTPFDNKIV VYKGDVYNMD YPPFGAGRPG QFGDIQSRTP ESKDVYANTQ LVLQRPAAGT VHVPYSQAPS GF KYWLKER GASLQHTAPF GCQIATNPVR AVNCAVGNMP ISIDIPEAAF TRVVDAPSLT DMSCEVPACT HSSDFGGVAV IKY AASKKG KCAVHSMTNA VTIREAEIEV EGNSQLQISF STALASAEFR VQVCSTQVHC AAECHPPKDH IVNYPASHTT LGVQ DISAT AMSWVQKITG GVGLVVAVAA LILIVVLCVS FSRH

UniProtKB: Structural polyprotein

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Macromolecule #4: Structural polyprotein

MacromoleculeName: Structural polyprotein / type: protein_or_peptide / ID: 4 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Chikungunya virus
Molecular weightTheoretical: 46.909578 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: NFNVYKATRP YLAHCPDCGE GHSCHSPVAL ERIRNEATDG TLKIQVSLQI GIKTDDSHDW TKLRYMDNHM PADAERAGLF VRTSAPCTI TGTMGHFILA RCPKGETLTV GFTDSRKISH SCTHPFHHDP PVIGREKFHS RPQHGKELPC STYVQSTAAT T EEIEVHMP ...String:
NFNVYKATRP YLAHCPDCGE GHSCHSPVAL ERIRNEATDG TLKIQVSLQI GIKTDDSHDW TKLRYMDNHM PADAERAGLF VRTSAPCTI TGTMGHFILA RCPKGETLTV GFTDSRKISH SCTHPFHHDP PVIGREKFHS RPQHGKELPC STYVQSTAAT T EEIEVHMP PDTPDRTLMS QQSGNVKITV NGQTVRYKCN CGGSNEGLTT TDKVINNCKV DQCHAAVTNH KKWQYNSPLV PR NAELGDR KGKIHIPFPL ANVTCRVPKA RNPTVTYGKN QVIMLLYPDH PTLLSYRNMG EEPNYQEEWV MHKKEVVLTV PTE GLEVTW GNNEPYKYWP QLSTNGTAHG HPHEIILYYY ELYPTMTVVV VSVASFVLLS MVGVAVGMCM CARRRCITPY ELTP GATVP FLLSLICCIR TAKA

UniProtKB: Structural polyprotein

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Macromolecule #5: CHIKV capsid protein

MacromoleculeName: CHIKV capsid protein / type: protein_or_peptide / ID: 5 / Number of copies: 4 / Enantiomer: LEVO / EC number: togavirin
Source (natural)Organism: Chikungunya virus
Molecular weightTheoretical: 16.428607 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
NDCIFEVKHE GKVTGYACLV GDKVMKPAHV KGTIDNADLA KLAFKRSSKY DLECAQIPVH MKSDASKFTH EKPEGYYNWH HGAVQYSGG RFTIPTGAGK PGDSGRPIFD NKGRVVAIVL GGANEGARTA LSVVTWNKDI VTKITPEGAE EW

UniProtKB: Structural polyprotein

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Macromolecule #11: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 11 / Number of copies: 4 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

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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: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination 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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Image processing

CTF correctionType: PHASE FLIPPING ONLY
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.73 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 491507
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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Atomic model buiding 1

Initial model
PDB IDChain

source_name: PDB, initial_model_type: experimental model

source_name: PDB, initial_model_type: experimental model
RefinementSpace: REAL / Protocol: RIGID BODY FIT
Output model

PDB-9iyi:
VLP structure of Chikungunya virus complexed with C34 Fab, 2f block.

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