Fig. 4: Structural mimicry is a feature of ESK1 off-target activity.
From: The physiological interactome of TCR-like antibody therapeutics in human tissues
A Overlay of RMFPNAPYL (purple, from X-ray structure with PDB ID 4WUU) with models of the confirmed cross-reactive peptides in the presence of the Fab of ESK1. The HLA-A*02:01 peptide binding groove is indicated in gray. The numbers indicate the approximate position of the amino acid side chain at the respective peptide position. B RMFPNAPYL peptide within the HLA-A*02:01 binding groove and interactions with the ESK1 Fab (PDB ID 4WUU). C Non-bonded interactions between the Fab of ESK1 and RMFPNAPYL (gray) in the HLA-A*02:01 peptide-HLA complex (X-ray crystal structure with PDB ID 4WUU). Models of the cross-reactive peptides SHC1469-477 (cyan) and RBM4B59-67 (orange) are shown for comparison. D Overlay of RMFPNAPYL peptide (purple, from X-ray structure with PDB ID 4WUU) with modeled RBM4B59-67 peptide (cyan) in the peptide binding groove of HLA-A*02:01.
