Neutralizing antibody to human rhinovirus 14 penetrates the receptor-binding canyon.
The three-dimensional structure of intact human rhinovirus 14 (HRV-14) complexed with Fab fragments (Fab17-IA) from a strongly neutralizing antibody that binds bivalently to the virion has been determined to 4.0 angstrom resolution by a combination of X-ray crystallography and cryo-electron microscopy. In contradiction to the most commonly held model of antibody-mediated neutralization, Fab17-IA does not induce a conformational change in the HRV-14 capsid. Instead, the paratope of the antibody undergoes a large conformational change to accommodate the epitope. Unlike any previously described antibody-antigen structure, the conserved framework region of the antibody makes extensive contact with the viral surface. Fab17-IA penetrates deep within the canyon in which the cellular receptor for HRV-14 binds. Hence, it is unlikely that viral quaternary structure evolves merely to evade immune recognition. Instead, the shape and position of the receptor-binding region on a virus probably dictates receptor binding and subsequent uncoating events and has little or no influence on concealing the virus from the immune system.
Smith
T J
TJ
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392, USA. tom@bragg.bio.purdue.edu
Chase
E S
ES
Schmidt
T J
TJ
Olson
N H
NH
Baker
T S
TS
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000914:Antibodies, Viral / Q000737:chemistry* / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D001666:Binding Sites, Antibody; D002213:Capsid / Q000737:chemistry / Q000276:immunology; D018360:Crystallography, X-Ray; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry; D008958:Models, Molecular; D009500:Neutralization Tests; D011487:Protein Conformation; D012229:Rhinovirus / Q000737:chemistry* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D018985:Epitopes, B-Lymphocyte; D007140:Immunoglobulin Fab Fragments; D018799:Intercellular Adhesion Molecule-1