7KCR

Cryo-EM structure of Zika virus in complex with E protein cross-linking human monoclonal antibody ADI30056

Summary for 7KCR

• Entry DOI: 10.2210/pdb7kcr/pdb
• EMDB information: 22818
• Descriptor: ADI30056 Fab heavy chain variable region, ADI30056 Fab light chain variable region, envelope protein E, ... (5 entities in total)
• Functional Keywords: zika virus, flavivirus, zika-antibody, virus-immune system complex, virus/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 214176.87

Authors

Sevvana, M.,Rogers, T.F.,Miller, A.S.,Long, F.,Klose, T.,Beutler, N.,Lai, Y.C.,Parren, M.,Walker, L.M.,Buda, G.,Burton, D.R.,Rossmann, M.G.,Kuhn, R.J. (deposition date: 2020-10-07, release date: 2020-12-16, Last modification date: 2024-11-13)

Primary citation

Sevvana, M.,Rogers, T.F.,Miller, A.S.,Long, F.,Klose, T.,Beutler, N.,Lai, Y.C.,Parren, M.,Walker, L.M.,Buda, G.,Burton, D.R.,Rossmann, M.G.,Kuhn, R.J.
Structural Basis of Zika Virus Specific Neutralization in Subsequent Flavivirus Infections.
Viruses, 12:-, 2020

PubMed Abstract: Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the virus surface, inhibiting conformational changes required for the formation of infectious fusogenic trimers similar to the hMAb, ZIKV-117. Structure-based functional analysis, and structure and sequence comparisons, identified ZIKV residues essential for neutralization and crucial for the evolution of highly potent E protein crosslinking Abs in ZIKV. Thus, this epitope, ZIKV's "Achilles heel", defined by the contacts between ZIKV and ADI-30056, could be a suitable target for the design of therapeutic antibodies.

PubMed: 33255202
DOI: 10.3390/v12121346

Experimental method

ELECTRON MICROSCOPY (4 Å)