Computational design of a synthetic PD-1 agonist
Cassie M. Bryan, Gabriel J. Rocklin, Matthew J. Bick, Alex Ford, Sonia Majri-Morrison, Ashley V. Kroll, Chad J. Miller, Lauren Carter, Inna Goreshnik, Alex Kang, Frank DiMaio, Kristin V. Tarbell, David Baker
Abstract
of ∼100 nM. The apo crystal structure shows that the binder folds as designed with a backbone RMSD of 1.3 Å to the design model. Trimerization of PD-MP1 resulted in a PD-1 agonist that strongly inhibits murine T cell activation. This small, hyperstable PD-1 binding protein was computationally designed with an all-beta interface, and the trimeric agonist could contribute to treatments for autoimmune and inflammatory diseases.
Topics & Concepts
AgonistProgrammed cell death 1AntibodyProgrammed cell deathPD-L1CancerChemistryComputational biologyCancer researchMedicineImmunotherapyReceptorImmunologyBiologyInternal medicineBiochemistryApoptosisCancer Immunotherapy and BiomarkersPeptidase Inhibition and AnalysisMonoclonal and Polyclonal Antibodies Research