Semisynthetic Viral Inhibitor for Light Control of the MHC I Peptide Loading Complex

Abstract: The immune system detects virally or malignantly transformed cells via peptide‐loaded major histocompatibility complex class I (pMHC I) molecules on the cell surface. MHC I molecules are loaded with cargo peptides in the endoplasmic reticulum (ER) by the highly dynamic multiprotein peptide loading complex (PLC). Here, we developed a semisynthetic approach to generate a photocleavable immune modulator ICP47 of Herpes simplex virus. Using this nanotool, we revealed key mechanistic events of the purified PLC, such as peptide binding and translocation coupled to ATP hydrolysis, triggered by light. We established a single‐organelle flow cytometry assay to monitor light‐controlled activation of the antigen processing machinery in native ER membranes. This photochemical modulation opens new opportunities for a comprehensive mechanistic analysis of the antigen processing machinery in vitro and native membrane environment.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Semisynthetic Viral Inhibitor for Light Control of the MHC I Peptide Loading Complex ; day:28 ; month:10 ; year:2022 ; extent:1
Angewandte Chemie / International edition. International edition ; (28.10.2022) (gesamt 1)

Creator
Winter, Christian
Domnick, Alexander
Cernova, Darja
Tampé, Robert

DOI
10.1002/anie.202211826
URN
urn:nbn:de:101:1-2022102915033887549668
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:34 AM CEST

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