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The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I.
- Source :
-
ELife [Elife] 2023 Jun 22; Vol. 12. Date of Electronic Publication: 2023 Jun 22. - Publication Year :
- 2023
-
Abstract
- Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). UGGT1 reglucosylates non-native glycoproteins and thereby allows them to revisit the ER folding machinery. Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation.<br />Competing Interests: LS, CW, IR, MZ, CT, RT No competing interests declared<br /> (© 2023, Sagert et al.)
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 37345806
- Full Text :
- https://doi.org/10.7554/eLife.85432