X ‐ray crystal structure localizes the mechanism of inhibition of an IL‐36R antagonist monoclonal antibody to interaction with Ig1 and Ig2 extra cellular domains

We report here the molecular structure of a complex between an extracellular portion of human IL‐36R and a Fab derived from a high affinity anti‐IL‐36R neutralizing monoclonal antibody at 2.3 Å resolution. This stru cture, the first of IL‐36R, reveals similarities with other structurally characterized IL‐1R family members and elucidates the molecular determinants leading to the high affinity binding of the monoclonal antibody. The structure of the complex reveals that the epitope recognized by the Fab is re mote from both the putative ligand and accessory protein binding interfaces on IL‐36R, suggesting that the functional activity of the antibody is noncompetitive for these binding events.

Source: Protein Science - June 23, 2020 Category: Biochemistry Authors: Eric T. Larson, Debra L. Brennan, Eugene R. Hickey, Raj Ganesan, Rachel Kroe ‐Barrett, Neil A. Farrow Tags: PROTEIN STRUCTURE REPORTS Source Type: research