The ER Aminopeptidases, ERAP1 and ERAP2, synergize to self-modulate their respective activities.

ABSTRACT:

Introduction

Critical steps in Major Histocompatibility Complex Class I (MHC-I) antigen presentation occur in the endoplasmic reticulum (ER). In general, peptides that enter the ER are longer than the optimal length for MHC-I binding. The final trimming of MHC-I epitopes is performed by two related aminopeptidases, ERAP1 and ERAP2 in humans that possess unique and complementary substrate trimming specificities. While ERAP1 efficiently trims peptides longer than 9 residues, ERAP2 preferentially trims peptides shorter than 9 residues.

Materials and methods

Using a combination of biochemical and proteomic studies followed by biological verification.

Results

We demonstrate that the optimal ligands for either enzyme act as inhibitors of the other enzyme. Specifically, the

SUBMITTER: Martin-Esteban A 

PROVIDER: S-EPMC9774488 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature