5H32: Cryo-em Structure Of Zika Virus Complexed With Fab C10 At Ph 5.0

Citation:
Abstract
The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barre syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late endosomal (pH5.0) environments. The 4.0 A resolution pH8.0 complex structure shows that the antibody binds to E proteins residues at the intra-dimer interface, and the virus quaternary structure-dependent inter-dimer and inter-raft interfaces. At pH6.5, antibody C10 locks all virus surface E proteins, and at pH5.0, it locks the E protein raft structure, suggesting that it prevents the structural rearrangement of the E proteins during the fusion event-a vital step for infection. This suggests antibody C10 could be a good therapeutic candidate.
PDB ID: 5H32Download
MMDB ID: 145241
PDB Deposition Date: 2016/10/20
Updated in MMDB: 2016/12
Experimental Method:
electron microscopy
Resolution: 12  Å
Source Organism:
Zika virus
Similar Structures:
Molecular Components in 5H32
Label Count Molecule
Proteins (9 molecules)
3
Structural Protein E
Molecule annotation
3
C10 IGG Heavy Chain Variable Region
Molecule annotation
3
C10 IGG Light Chain Variable Region
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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