5h30 | pdb_00005h30

Cryo-EM structure of zika virus complexed with Fab C10 at pH 6.5

Loading... Status: waiting for Mol* initialization Structural highlights 5h30 is a 12 chain structure with sequence from Human and Zika virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 5h32, 5h37 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Neutralization mechanism of a highly potent antibody against Zika virus.,Zhang S, Kostyuchenko VA, Ng TS, Lim XN, Ooi JS, Lambert S, Tan TY, Widman DG, Shi J, Baric RS, Lok SM Nat Commun. 2016 Nov 24;7:13679. doi: 10.1038/ncomms13679. PMID:27882950 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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