5KVD

Zika specific antibody, ZV-2, bound to ZIKA envelope DIII

Summary for 5KVD

• Entry DOI: 10.2210/pdb5kvd/pdb
• Related: 5KVE 5KVF 5KVG
• Descriptor: Zika Envelope DIII, ZV-2 Antibody Fab Light Chain, ZV-2 Antibody Fab Heavy Chain, ... (7 entities in total)
• Functional Keywords: zika virus, envelope diii, viral protein, antibody, igg2c, structural genomics, center for structural genomics of infectious diseases, csgid., viral protein-immune system complex, viral protein/immune system
• Biological source: Zika virus (ZIKV); More
• Cellular location: Virion membrane ; Multi-pass membrane protein : A0A024B7W1
• Total number of polymer chains: 3
• Total formula weight: 60344.52

Authors

Zhao, H.,Nelson, C.A.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2016-07-14, release date: 2016-08-03, Last modification date: 2024-10-23)

Primary citation

Zhao, H.,Fernandez, E.,Dowd, K.A.,Speer, S.D.,Platt, D.J.,Gorman, M.J.,Govero, J.,Nelson, C.A.,Pierson, T.C.,Diamond, M.S.,Fremont, D.H.
Structural Basis of Zika Virus-Specific Antibody Protection.
Cell, 166:1016-1027, 2016

PubMed Abstract: Zika virus (ZIKV) infection during pregnancy has emerged as a global public health problem because of its ability to cause severe congenital disease. Here, we developed six mouse monoclonal antibodies (mAbs) against ZIKV including four (ZV-48, ZV-54, ZV-64, and ZV-67) that were ZIKV specific and neutralized infection of African, Asian, and American strains to varying degrees. X-ray crystallographic and competition binding analyses of Fab fragments and scFvs defined three spatially distinct epitopes in DIII of the envelope protein corresponding to the lateral ridge (ZV-54 and ZV-67), C-C' loop (ZV-48 and ZV-64), and ABDE sheet (ZV-2) regions. In vivo passive transfer studies revealed protective activity of DIII-lateral ridge specific neutralizing mAbs in a mouse model of ZIKV infection. Our results suggest that DIII is targeted by multiple type-specific antibodies with distinct neutralizing activity, which provides a path for developing prophylactic antibodies for use in pregnancy or designing epitope-specific vaccines against ZIKV.

PubMed: 27475895
DOI: 10.1016/j.cell.2016.07.020

Experimental method

X-RAY DIFFRACTION (1.65 Å)