Oral Presentation The 47th Lorne Conference on Protein Structure and Function 2022

Machineries and Supercomplexes in Cellular Quality Control and Adaptive Immunity (#38)

Robert Tampé 1
  1. Biocenter, Goethe University Frankfurt, Frankfurt/M., HESSEN, Germany

Folding and assembly of proteins in secretory pathways are mediated by a sophisticated chaperone and quality control network whose structural and mechanistic organization is largely unknown. The peptide loading complex (PLC) plays a fundamental role in the biogenesis of MHC I molecules, orchestrating the adaptive immune response against pathogens, vaccines, and cancer1,2. Any misinterpretation can lead to inflammation and autoimmune disease. By using an integrative approach, we explore the cellular pathways, dynamic assemblies, and macromolecular membrane machineries in antigen processing and in view of viral and tumor immune evasion3-5. The conformational landscape and the mechanism of intracellular antigen translocation as well as MHC I quality control and immune evasion complexes will be illuminated.

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  3. Blees, A. et al. Structure of the human MHC-I peptide-loading complex. Nature 551, 525-528 (2017).
  4. Thomas, C. & Tampé, R. Structure of the TAPBPR-MHC I complex defines the mechanism of peptide loading and editing. Science 358, 1060-1064 (2017).
  5. Hofmann, S. et al. Conformation space of a heterodimeric ABC exporter under turnover conditions. Nature 571, 580-583 (2019).