title: ERAP1-ERAP2 dimerization increases peptide-trimming efficiency.
abstract: The endoplasmic reticulum aminopeptidases (ERAP)1 and ERAP2 play a critical role in the production of final epitopes presented by MHC class I molecules. Formation of heterodimers by ERAP1 and ERAP2 has been proposed to facilitate trimming of epitope precursor peptides, but the effects of dimerization on ERAP function remain unknown. In this study, we produced stabilized ERAP1-ERAP2 heterodimers and found that they produced several mature epitopes more efficiently than a mix of the two enzymes unable to dimerize. Physical interaction with ERAP2 changes basic enzymatic parameters of ERAP1 and improves its substrate-binding affinity. Thus, by bringing the two enzymes in proximity and by producing allosteric effects on ERAP1, dimerization of ERAP1/2 creates complexes with superior peptide-trimming efficacy. Such complexes are likely to enhance Ag presentation by cells displaying coordinated expression of the two enzymes.
authors.affiliation: INSERM Unité 1151, 75015 Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8253, 75015 Paris, France; and Faculté de Medicine, Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.
authors.forename: Irini
authors.initials: I
authors.lastname: Evnouchidou
authors.affiliation: INSERM Unité 1151, 75015 Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8253, 75015 Paris, France; and Faculté de Medicine, Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Weimershaus
authors.affiliation: INSERM Unité 1151, 75015 Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8253, 75015 Paris, France; and Faculté de Medicine, Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.
authors.forename: Loredana
authors.initials: L
authors.lastname: Saveanu
authors.affiliation: INSERM Unité 1151, 75015 Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8253, 75015 Paris, France; and Faculté de Medicine, Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France peter.van-endert@inserm.fr.
authors.forename: Peter
authors.initials: P
authors.lastname: van Endert
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D055503:Protein Multimerization; D061987:Sf9 Cells; D013379:Substrate Specificity
chemical_list: D000939:Epitopes; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D000626:Aminopeptidases; C464841:ERAP1 protein, human; C503944:ERAP2 protein, human