The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I
© 2023, Sagert et al..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
eLife - 12(2023) vom: 22. Juni |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sagert, Lina [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.07.2023 Date Revised 16.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.7554/eLife.85432 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 4 | |a The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023, Sagert et al. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ER quality control | |
| 650 | 4 | |a MHC I chaperones | |
| 650 | 4 | |a adaptive immunity | |
| 650 | 4 | |a antigen processing | |
| 650 | 4 | |a biochemistry | |
| 650 | 4 | |a chemical biology | |
| 650 | 4 | |a glycoproteins | |
| 650 | 4 | |a human | |
| 650 | 4 | |a immunology | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a peptide editing | |
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| 650 | 7 | |a Immunoglobulins |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Molecular Chaperones |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 650 | 7 | |a UGGT1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.4.1.- |2 NLM | |
| 650 | 7 | |a TAPBPL protein, human |2 NLM | |
| 700 | 1 | |a Winter, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Ruppert, Ina |e verfasserin |4 aut | |
| 700 | 1 | |a Zehetmaier, Maximilian |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Tampé, Robert |e verfasserin |4 aut | |
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