High Resolution Structure and Neutralization Mechanism of 1G1 Fab Bound to Poliovirus Type 3
Restricted (Penn State Only)
Author:
Faust, Julia
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Susan Hafenstein, Thesis Supervisor Timothy Charles Meredith, Thesis Honors Advisor
Keywords:
CryoEM poliovirus SPV3 virology neutralizing antibody 1G1 Fab structural biology
Abstract:
Poliovirus is a highly contagious pathogen that is causes acute flaccid paralysis in the central nervous system. Previously, a panel of twelve cross-neutralizing antibodies was characterized. An antibody fragment (Fab) of monoclonal 1G1 antibody was found to neutralize Sabin-attenuated Poliovirus Type 3 (SPV3). Using cryo-electron microscopy (cryo-EM), the resolution of 1G1-Fab-SPV3 complex was solved to 2.39Å resolution. The near-atomic resolution of the complex allowed for de-novo building of the 1G1 Fab structure into the electron density. Using this, the footprint of the Fab was able to be determined and showed overlap with key antigenic sites on the poliovirus capsid. Furthermore, it was determined that the Fab bound monovalently to the capsid and caused no conformational changed upon binding. This suggests that the mechanism for neutralization used by this antibody is inhibition of viral uncoating through hyper stabilization and viral aggregation through crosslinking of the antibodies.
