title: West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody.
abstract: Flaviviruses, such as West Nile virus (WNV), are significant human pathogens. The humoral immune response plays an important role in the control of flavivirus infection and disease. The structure of WNV complexed with the Fab fragment of the strongly neutralizing mAb E16 was determined to 14.5-Angstrom resolution with cryo-electron microscopy. E16, an antibody with therapeutic potential, binds to domain III of the WNV envelope glycoprotein. Because of steric hindrance, Fab E16 binds to only 120 of the 180 possible binding sites on the viral surface. Fitting of the previously determined x-ray structure of the Fab-domain III complex into the cryo-electron microscopy density required a change of the elbow angle between the variable and constant domains of the Fab. The structure suggests that the E16 antibody neutralizes WNV by blocking the initial rearrangement of the E glycoprotein before fusion with a cellular membrane.
authors.affiliation: Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907-2054, USA.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Kaufmann
authors.forename: Grant E
authors.initials: GE
authors.lastname: Nybakken
authors.forename: Paul R
authors.initials: PR
authors.lastname: Chipman
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kuhn
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rossmann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000648:ultrastructure; D001665:Binding Sites; D002460:Cell Line; D006224:Cricetinae; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008958:Models, Molecular; D011487:Protein Conformation; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D014902:West Nile virus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D014760:Viral Fusion Proteins