Objetivo Our body constantly encounters pathogens or malignant transformation. Consequently, the adaptive immune system is in place to eliminate infected or cancerous cells. Specific immune reactions are triggered by selected peptide epitopes presented on major histocompatibility complex class I (MHC-I) molecules, which are scanned by cytotoxic T lymphocytes.Intracellular transport, loading, and editing of antigenic peptides onto MHC-I are coordinated by a highly dynamic multisubunit peptide-loading complex (PLC) in the ER membrane. This multitasking machinery orchestrates the translocation of proteasomal degradation products into the ER as well as the loading and proofreading of MHC-I molecules.Sampling of myriads of different peptide/MHC-I allomorphs requires a precisely coordinated quality control network in a single macromolecular assembly, including the transporter associated with antigen processing TAP1/2, the MHC-I heterodimer, the oxidoreductase ERp57, and the ER chaperones tapasin and calreticulin. Proofreading by MHC-I editing complexes guarantees that only very stable peptide/MHC-I complexes are released to the cell surface.This proposal aims to gain a holistic understanding of the PLC and MHC-I proofreading complexes, which are essential for cellular immunity. We strive to elucidate the mechanistic basis of the antigen translocation complex TAP as well as the MHC-I chaperone complexes within the PLC. This high-risk/high-gain project will define the inner working of the PLC, which constitutes the central machinery of immune surveillance in health and diseases. The results will provide detailed insights into the architecture and dynamics of the PLC and will ultimately pave the way for unraveling general principles of intracellular membrane-embedded multiprotein assemblies in the human body. Furthermore, we will deliver a detailed understanding of mechanisms at work in viral immune evasion. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesmedical and health sciencesbasic medicineimmunology Palabras clave Membrane Proteins Macromolecular Complexes ER Quality Control Membrane Transporters Fluorescence Labeling Chemical Biology Super-resolution Microscopy Programa(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Tema(s) ERC-2017-ADG - ERC Advanced Grant Convocatoria de propuestas ERC-2017-ADG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-ADG - Advanced Grant Institución de acogida JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN Aportación neta de la UEn € 2 181 250,00 Dirección THEODOR W ADORNO PLATZ 1 60323 Frankfurt Am Main Alemania Ver en el mapa Región Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 2 181 250,00 Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN Alemania Aportación neta de la UEn € 2 181 250,00 Dirección THEODOR W ADORNO PLATZ 1 60323 Frankfurt Am Main Ver en el mapa Región Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 2 181 250,00