Redox regulation of peptide receptivity of major histocompatibility complex class i molecules by erp57 and tapasin

ABSTRACT The function of the oxidoreductase ERp57 in the major histocompatibility complex (MHC) class I peptide-loading complex has remained elusive. Here we show that in the absence of

tapasin, the α2 disulfide bond in the MHC class I peptide-binding groove was rapidly reduced. Covalent sequestration of ERp57 by tapasin was needed to protect the α2 disulfide bond against

reduction and thus to maintain the binding groove in a peptide-receptive state. Allelic variations in MHC class I tapasin dependency reflected their susceptibility to reduction of the α2

disulfide bond. In the absence of sequestration, ERp57 acted directly on the α2 disulfide bond. Our work provides insight into how the immune system customizes 'quality control' in

the endoplasmic reticulum to fit the needs of antigen presentation. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution

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about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS STRUCTURE OF AN MHC I–TAPASIN–ERP57 EDITING COMPLEX DEFINES CHAPERONE

PROMISCUITY Article Open access 14 September 2022 EXCHANGE CATALYSIS BY TAPASIN EXPLOITS CONSERVED AND ALLELE-SPECIFIC FEATURES OF MHC-I MOLECULES Article Open access 09 July 2021 MOLECULAR

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references ACKNOWLEDGEMENTS We thank C. Mader for expert technical assistance; F. Momburg, N. Garbi and N. Bangia (Roswell Park Cancer Institute) for discussions; and F. Momburg and P.

Cresswell (Yale University) for reagents. Supported by the Deutsche Forschungsgemeinschaft (DI 731/2-1) and the European Commission (Marie Curie Excellence Grant). AUTHOR INFORMATION AUTHORS

AND AFFILIATIONS * Redox Regulation Research Group, German Cancer Research Center, Heidelberg, D-69120, Germany Alexandra Kienast, Marc Preuss, Monique Winkler & Tobias P Dick Authors *

Alexandra Kienast View author publications You can also search for this author inPubMed Google Scholar * Marc Preuss View author publications You can also search for this author inPubMed 

Google Scholar * Monique Winkler View author publications You can also search for this author inPubMed Google Scholar * Tobias P Dick View author publications You can also search for this

author inPubMed Google Scholar CONTRIBUTIONS T.P.D. designed the research, supervised the experiments, analyzed data and wrote the manuscript; A.K. designed experiments, did most

experiments, analyzed data and contributed to the writing of the manuscript; M.P. did PDI experiments; and M.W. contributed to ERp57 depletion experiments. CORRESPONDING AUTHOR

Correspondence to Tobias P Dick. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES

Supplementary Figures 1–5 (PDF 1890 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kienast, A., Preuss, M., Winkler, M. _et al._ Redox regulation of

peptide receptivity of major histocompatibility complex class I molecules by ERp57 and tapasin. _Nat Immunol_ 8, 864–872 (2007). https://doi.org/10.1038/ni1483 Download citation * Received:

26 October 2006 * Accepted: 30 May 2007 * Published: 01 July 2007 * Issue Date: August 2007 * DOI: https://doi.org/10.1038/ni1483 SHARE THIS ARTICLE Anyone you share the following link with

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