1ZTX

West Nile Virus Envelope Protein DIII in complex with neutralizing E16 antibody Fab

Summary for 1ZTX

• Entry DOI: 10.2210/pdb1ztx/pdb
• Descriptor: Envelope protein, Heavy Chain of E16 Antibody, Light Chain of E16 Antibody, ... (4 entities in total)
• Functional Keywords: antibody, fab, neutralizing, virus, envelope, viral protein-immune system complex, viral protein/immune system
• Biological source: West Nile virus; More
• Cellular location: Envelope protein E: Virion membrane; Multi- pass membrane protein: Q91KZ4
• Total number of polymer chains: 3
• Total formula weight: 58140.67

Authors

Nybakken, G.E.,Oliphant, T.,Diamond, M.S.,Fremont, D.H. (deposition date: 2005-05-27, release date: 2005-10-04, Last modification date: 2024-10-30)

Primary citation

Nybakken, G.E.,Oliphant, T.,Johnson, S.,Burke, S.,Diamond, M.S.,Fremont, D.H.
Structural basis of West Nile virus neutralization by a therapeutic antibody.
Nature, 437:764-769, 2005

PubMed Abstract: West Nile virus is a mosquito-borne flavivirus closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses. In establishing infection these icosahedral viruses undergo endosomal membrane fusion catalysed by envelope glycoprotein rearrangement of the putative receptor-binding domain III (DIII) and exposure of the hydrophobic fusion loop. Humoral immunity has an essential protective function early in the course of West Nile virus infection. Here, we investigate the mechanism of neutralization by the E16 monoclonal antibody that specifically binds DIII. Structurally, the E16 antibody Fab fragment engages 16 residues positioned on four loops of DIII, a consensus neutralizing epitope sequence conserved in West Nile virus and distinct in other flaviviruses. The E16 epitope protrudes from the surface of mature virions in three distinct environments, and docking studies predict Fab binding will leave five-fold clustered epitopes exposed. We also show that E16 inhibits infection primarily at a step after viral attachment, potentially by blocking envelope glycoprotein conformational changes. Collectively, our results suggest that a vaccine strategy targeting the dominant DIII epitope may elicit safe and effective immune responses against flaviviral diseases.

PubMed: 16193056
DOI: 10.1038/nature03956

Experimental method

X-RAY DIFFRACTION (2.5 Å)