Noncompetitive Allosteric Antagonism of Death Receptor 5 by a Synthetic Affibody Ligand.

ABSTRACT: Fatty acid-induced upregulation of death receptor 5 (DR5) and its cognate ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), promotes hepatocyte lipoapoptosis, which is a key mechanism in the progression of fatty liver disease. Accordingly, inhibition of DR5 signaling represents an attractive strategy for treating fatty liver disease. Ligand competition strategies are prevalent in tumor necrosis factor receptor antagonism, but recent studies have suggested that noncompetitive inhibition through perturbation of the receptor conformation may be a compelling alternative. To this end, we used yeast display and a designed combinatorial library to identify a synthetic 58-amino acid affibody ligand that specifically binds DR5. Biophysical and biochemical studies show that th

SUBMITTER: Vunnam N 

PROVIDER: S-EPMC7658720 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature