Structural Basis of Inhibition of Perforin Mediated Cytolysis, and the uPA/uPAR System in Cancer using cryo-EM

Perforin and uPAR are two small human proteins involved in immunity and cancer respectively. The thesis determined atomic structures of perforin soluble oligomer, and perforin or uPAR in complex with their respective therapeutic antibodies. The thesis identifies key intermolecular interactions and critical residues for perforin oligomer assembly and pore formation, providing a foundation for treatment strategies aimed at modulating perforin-mediated immune diseases. The thesis also identified critical uPAR residues that can be targeted for developing treatment strategies, and offers structural evidence for potential co-administration of a therapeutic anti-uPAR antibody and positron radionuclide labelled peptide for treatment and imaging of cancers.