5H32

Cryo-EM structure of zika virus complexed with Fab C10 at pH 5.0

Summary for 5H32

• Entry DOI: 10.2210/pdb5h32/pdb
• Related: 5H30 5H37
• EMDB information: 9574
• Descriptor: structural protein E, C10 IgG heavy chain variable region, C10 IgG light chain variable region (3 entities in total)
• Functional Keywords: antibody, virus-immune system complex, virus/immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Virion membrane ; Multi-pass membrane protein : A0A024B7W1
• Total number of polymer chains: 9
• Total formula weight: 209566.05

Authors

Zhang, S.,Kostyuchenko, V.,Ng, T.-S.,Lok, S.-M. (deposition date: 2016-10-20, release date: 2016-11-30, Last modification date: 2024-05-29)

Primary citation

Zhang, S.,Kostyuchenko, V.A.,Ng, T.-S.,Lim, X.-N.,Ooi, J.S.G.,Lambert, S.,Tan, T.Y.,Widman, D.G.,Shi, J.,Baric, R.S.,Lok, S.-M.
Neutralization mechanism of a highly potent antibody against Zika virus
Nat Commun, 7:13679-13679, 2016

PubMed Abstract: The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré 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 Å 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.

PubMed: 27882950
DOI: 10.1038/ncomms13679

Experimental method

ELECTRON MICROSCOPY (12 Å)