This is a 3D print of a humanized monoclonal IgG4 antibody used in multiple types of cancer treatments. Protein is visualized to distinguish each chain of the antibody in different shades of green and PD-1 red. Biologic model was created from PDB IDs: 5dk3
and 3D printed in full-color sandstone.
Immunoglobulin G4 antibodies exhibit unusual properties with important biological consequences. Pembrolizumab is a compact molecule, consistent with the presence of a short hinge region. The Fc domain is glycosylated at the CH2 domain on both chains, but one CH2 domain is rotated 120° with respect to the conformation observed in all reported structures to date, and its glycan chain faces the solvent. The structure suggests a role for the S228P mutation in preventing the IgG4 arm exchange. In addition, this unusual Fc conformation suggests possible structural diversity between IgG subclasses and shows that use of isolated antibody fragments could mask potentially important interactions, owing to molecular flexibility.