Browsing by Subject "antigen processing"

Now showing 1 - 1 of 1
  • Research Data
    Reconstitution of glycan-driven MHC I recycling reveals calreticulin as mediator between TAPBPR and tapasin
    2025-04-24
    Heinke, Tim Julius 
    Fahim, Amin 
    Popovic, Niko
    Rath, Tobias
    Morgner, Nina
    Trowitzsch, Simon
    Tampé, Robert
    Heinke, Tim Julius  (DataCollector)
    Fahim, Amin  (DataCollector)
    Trowitzsch, Simon (ContactPerson)
    Tampé, Robert (ContactPerson)
    Popovic, Niko (DataCollector)
    Rath, Tobias (DataCollector)
    Morgner, Nina (ContactPerson)
    Protein folding in the endoplasmic reticulum (ER) is essential for about one-third of the mammalian proteome. N-linked glycosylation and subsequent glycan remodeling barcodes glycoproteins during their maturation in the ER. Major histocompatibility complex class I (MHC I) molecules, key for adaptive immunity, rely on a dedicated quality control cycle that involves specialized chaperones and glycan-modifying enzymes for their maturation and loading of immunogenic peptides. However, the functional interplay of the MHC I editors tapasin as part of the peptide-loading complex (PLC), TAP-binding protein-related (TAPBPR), the UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1), and calreticulin in glycan-dependent transfer of MHC I clients has not been determined in a reconstituted system. With isolated components, we show that transfer of peptide-receptive MHC I from the downstream quality control factor TAPBPR back to tapasin depends on the recognition of the monoglucosylated glycan of MHC I by calreticulin. While calreticulin’s C-terminal acidic helix is dispensable for disengaging reglucosylated MHC I from TAPBPR, it is essential for docking MHC I onto tapasin. Our data provide a mechanistic basis for glycan-surveillance by calreticulin necessary for retrograde trafficking of misfolded or suboptimally loaded MHC I that escaped the first quality control at the PLC and were trapped by TAPBPR. Such finetuned dynamic network of glycan-dependent and MHC I-specific chaperones guarantees maturation of MHC I molecules and highlight the fundamental processes driving ER protein quality control.
      52  7