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TitleStructural analyses at pseudo atomic resolution of Chikungunya virus and antibodies show mechanisms of neutralization.
Journal, issue, pagesElife, Vol. 2, Page e00435, Year 2013
Publish dateApr 2, 2013
AuthorsSiyang Sun / Ye Xiang / Wataru Akahata / Heather Holdaway / Pankaj Pal / Xinzheng Zhang / Michael S Diamond / Gary J Nabel / Michael G Rossmann /
PubMed AbstractA 5.3 Å resolution, cryo-electron microscopy (cryoEM) map of Chikungunya virus-like particles (VLPs) has been interpreted using the previously published crystal structure of the Chikungunya E1-E2 ...A 5.3 Å resolution, cryo-electron microscopy (cryoEM) map of Chikungunya virus-like particles (VLPs) has been interpreted using the previously published crystal structure of the Chikungunya E1-E2 glycoprotein heterodimer. The heterodimer structure was divided into domains to obtain a good fit to the cryoEM density. Differences in the T = 4 quasi-equivalent heterodimer components show their adaptation to different environments. The spikes on the icosahedral 3-fold axes and those in general positions are significantly different, possibly representing different phases during initial generation of fusogenic E1 trimers. CryoEM maps of neutralizing Fab fragments complexed with VLPs have been interpreted using the crystal structures of the Fab fragments and the VLP structure. Based on these analyses the CHK-152 antibody was shown to stabilize the viral surface, hindering the exposure of the fusion-loop, likely neutralizing infection by blocking fusion. The CHK-9, m10 and m242 antibodies surround the receptor-attachment site, probably inhibiting infection by blocking cell attachment. DOI:http://dx.doi.org/10.7554/eLife.00435.001.
External linksElife / PubMed:23577234 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.995 - 16.9 Å
Structure data

5576

3j2x

EMDB-5576, PDB-3j2x:
Electron Cryo-microscopy of Chikungunya VLP in complex with neutralizing antibody Fab m242
Method: EM (single particle) / Resolution: 15.6 Å

5577

3j2w

EMDB-5577, PDB-3j2w:
Electron cryo-microscopy of Chikungunya virus
Method: EM (single particle) / Resolution: 5.0 Å

5578

3j2y

EMDB-5578, PDB-3j2y:
Electron Cryo-microscopy of Chikungunya VLP in complex with neutralizing antibody Fab 9.8B
Method: EM (single particle) / Resolution: 14.9 Å

5579

3j2z

EMDB-5579, PDB-3j2z:
Electron Cryo-microscopy of Chikungunya VLP in complex with neutralizing antibody Fab m10
Method: EM (single particle) / Resolution: 16.9 Å

5580

3j30

EMDB-5580, PDB-3j30:
Electron Cryo-microscopy of Chikungunya VLP in complex with neutralizing antibody Fab CHK152
Method: EM (single particle) / Resolution: 16.0 Å

PDB-4gq9:
Chikungunya virus neutralizing antibody 9.8B Fab fragment
Method: X-RAY DIFFRACTION / Resolution: 2.995 Å

Source
  • Homo sapiens (human)
  • mus musculus (house mouse)
  • chikungunya virus
KeywordsVIRUS / E1-E2 glycoprotein / nucleocapsid protein / transmembrane helix / IMMUNE SYSTEM / Alpha virus / Chikungunya VLP / neutralizing antibody m242 / neutralizing antibody 9.8B / neutralizing antibody m10 / neutralizing antibody CHK152 / VIRAL PROTEIN / IgG fold / antibody

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