Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities

In this study, we report studies on structure-guided mutational and hydrolysis kinetics, and peptide trimming assays to further examine the functional roles of this SC subsite. Most strikingly, a point mutation V737R results in a change of substrate preference from a hydrophobic to a negatively charged PC anchor residue; the latter is presumed to be a poor substrate for WT ERAP1. These studies validate the crystallographic observations that this SC subsite is directly involved in binding and recognition of the substrate PC anchor and presents a potential target to modulate MHC-restricted immunopeptidomes.PMID:37858978 | DOI:10.1111/imm.13709

Source: Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Suchita Pande Hwai-Chen Guo Source Type: research