title: Structure of a neutralizing antibody bound monovalently to human rhinovirus 2.
abstract: The structure of a complex between human rhinovirus 2 (HRV2) and the Fab fragment of neutralizing monoclonal antibody (MAb) 3B10 has been determined to 25-A resolution by cryoelectron microscopy and three-dimensional reconstruction techniques. The footprint of 3B10 on HRV2 is very similar to that of neutralizing MAb 8F5, which binds bivalently across the icosahedral twofold axis. However, the 3B10 Fab fragment (Fab-3B10) is bound in an orientation, inclined at approximately 45 degrees to the surface of the virus capsid, which is compatible only with monovalent binding of the antibody. The canyon around the fivefold axis is not directly obstructed by the bound Fab. The X-ray structures of a closely related HRV (HRV1A) and a Fab fragment were fitted to the density maps of the HRV2-Fab-3B10 complex obtained by cryoelectron microscope techniques. The footprint of 3B10 on the viral surface is largely on VP2 but also covers the VP3 loop centered on residue 3064 and the VP1 loop centered on residue 1267. MAb 3B10 can interact directly with VP2 residue 2164, the site of an escape mutation on VP2, and with VP1 residues 1264 to 1267, the site of a deletion escape mutation. Deletion of these residues shortens the VP1 loop, moving it away from the MAb binding site. All structural and biochemical evidence indicates that MAb 3B10 binds to a conformation epitope on HRV2.
authors.affiliation: Institut de Biologie Structurale Jean-Pierre Ebel, Grenoble, France. HEWAT@IBS.FR
authors.forename: E A
authors.initials: EA
authors.lastname: Hewat
authors.forename: T C
authors.initials: TC
authors.lastname: Marlovits
authors.forename: D
authors.initials: D
authors.lastname: Blaas
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000914:Antibodies, Viral / Q000737:chemistry* / Q000276:immunology; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D009500:Neutralization Tests; D010849:Picornaviridae / Q000276:immunology; D011487:Protein Conformation; D012229:Rhinovirus / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral