Computational design of a synthetic PD-1 agonist.

ABSTRACT: Programmed cell death protein-1 (PD-1) expressed on activated T cells inhibits T cell function and proliferation to prevent an excessive immune response, and disease can result if this delicate balance is shifted in either direction. Tumor cells often take advantage of this pathway by overexpressing the PD-1 ligand PD-L1 to evade destruction by the immune system. Alternatively, if there is a decrease in function of the PD-1 pathway, unchecked activation of the immune system and autoimmunity can result. Using a combination of computation and experiment, we designed a hyperstable 40-residue miniprotein, PD-MP1, that specifically binds murine and human PD-1 at the PD-L1 interface with a K_d of ∼100 nM. The apo crystal structure shows that the binder folds as designed with a backbone

SUBMITTER: Bryan CM 

PROVIDER: S-EPMC8307378 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature