3N9G

Crystal structure of the Fab fragment of the human neutralizing anti-West Nile Virus MAb CR4354

Summary for 3N9G

• Entry DOI: 10.2210/pdb3n9g/pdb
• EMDB information: 5190
• Descriptor: Fab fragment of MAb CR4354, heavy chain, Fab fragment of MAb CR4354, light chain (3 entities in total)
• Functional Keywords: fab fragment, human neutralizing antibody, mab cr4354, immune system, anti-west nile virus
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 47653.86

Authors

Kaufmann, B.,Rossmann, M.G. (deposition date: 2010-05-29, release date: 2010-11-24, Last modification date: 2024-11-20)

Primary citation

Kaufmann, B.,Vogt, M.R.,Goudsmit, J.,Holdaway, H.A.,Aksyuk, A.A.,Chipman, P.R.,Kuhn, R.J.,Diamond, M.S.,Rossmann, M.G.
Neutralization of West Nile virus by cross-linking of its surface proteins with Fab fragments of the human monoclonal antibody CR4354.
Proc.Natl.Acad.Sci.USA, 107:18950-18955, 2010

PubMed Abstract: Many flaviviruses are significant human pathogens, with the humoral immune response playing an essential role in restricting infection and disease. CR4354, a human monoclonal antibody isolated from a patient, neutralizes West Nile virus (WNV) infection at a postattachment stage in the viral life-cycle. Here, we determined the structure of WNV complexed with Fab fragments of CR4354 using cryoelectron microscopy. The outer glycoprotein shell of a mature WNV particle is formed by 30 rafts of three homodimers of the viral surface protein E. CR4354 binds to a discontinuous epitope formed by protein segments from two neighboring E molecules, but does not cause any detectable structural disturbance on the viral surface. The epitope occurs at two independent positions within an icosahedral asymmetric unit, resulting in 120 binding sites on the viral surface. The cross-linking of the six E monomers within one raft by four CR4354 Fab fragments suggests that the antibody neutralizes WNV by blocking the pH-induced rearrangement of the E protein required for virus fusion with the endosomal membrane.

PubMed: 20956322
DOI: 10.1073/pnas.1011036107

Experimental method

X-RAY DIFFRACTION (1.434 Å)