ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing

ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing

The processing of MHC class I antigenic precursor peptides by the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 is an important event in the cell biology of antigen presentation. To date, the molecular context by which the ERAP enzymes trim precursor peptides, and how ERAPs shape peptide...

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Main Authors: Chen, Hanna, Li, Lenong, Weimershaus, Mirjana, Evnouchidou, Irini, van Endert, Peter, Bouvier, Marlene
Format: Online
Language:English
Published: Nature Publishing Group 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981824/
id pubmed-4981824
recordtype oai_dc
spelling pubmed-49818242016-08-19 ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing Chen, Hanna Li, Lenong Weimershaus, Mirjana Evnouchidou, Irini van Endert, Peter Bouvier, Marlene Article The processing of MHC class I antigenic precursor peptides by the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 is an important event in the cell biology of antigen presentation. To date, the molecular context by which the ERAP enzymes trim precursor peptides, and how ERAPs shape peptide repertoires, remain open questions. Using ERAP1 and ERAP2 heterodimers (ERAP1/2), and N-terminally extended model and natural peptides in their free and HLA-B*0801-bound forms, we characterized the mode of action of ERAPs. We provide evidence that ERAP1/2 can trim MHC I-bound precursor peptides to their correct and final lengths, albeit more slowly than the corresponding free precursors. Trimming of MHC I-bound precursors by ERAP1/2 increases the conformational stability of MHC I/peptide complexes. From the data, we propose a molecular mechanistic model of ERAP1/2 as peptide editors. Overall, our study provides new findings on a significant issue of the ERAP-mediated processing pathway of MHC class I antigens. Nature Publishing Group 2016-08-12 /pmc/articles/PMC4981824/ /pubmed/27514473 http://dx.doi.org/10.1038/srep28902 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Chen, Hanna
Li, Lenong
Weimershaus, Mirjana
Evnouchidou, Irini
van Endert, Peter
Bouvier, Marlene
spellingShingle Chen, Hanna
Li, Lenong
Weimershaus, Mirjana
Evnouchidou, Irini
van Endert, Peter
Bouvier, Marlene
ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing
author_facet Chen, Hanna
Li, Lenong
Weimershaus, Mirjana
Evnouchidou, Irini
van Endert, Peter
Bouvier, Marlene
author_sort Chen, Hanna
title ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing
title_short ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing
title_full ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing
title_fullStr ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing
title_full_unstemmed ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing
title_sort erap1-erap2 dimers trim mhc i-bound precursor peptides; implications for understanding peptide editing
description The processing of MHC class I antigenic precursor peptides by the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 is an important event in the cell biology of antigen presentation. To date, the molecular context by which the ERAP enzymes trim precursor peptides, and how ERAPs shape peptide repertoires, remain open questions. Using ERAP1 and ERAP2 heterodimers (ERAP1/2), and N-terminally extended model and natural peptides in their free and HLA-B*0801-bound forms, we characterized the mode of action of ERAPs. We provide evidence that ERAP1/2 can trim MHC I-bound precursor peptides to their correct and final lengths, albeit more slowly than the corresponding free precursors. Trimming of MHC I-bound precursors by ERAP1/2 increases the conformational stability of MHC I/peptide complexes. From the data, we propose a molecular mechanistic model of ERAP1/2 as peptide editors. Overall, our study provides new findings on a significant issue of the ERAP-mediated processing pathway of MHC class I antigens.
publisher Nature Publishing Group
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981824/
_version_ 1613626111567069184

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