7QPD
Structure of the human MHC I peptide-loading complex editing module
Summary for 7QPD
| Entry DOI | 10.2210/pdb7qpd/pdb |
| Related | 6ENY |
| EMDB information | 14119 |
| Descriptor | Beta-2-microglobulin, Tapasin, Protein disulfide-isomerase A3, ... (7 entities in total) |
| Functional Keywords | antigen processing, peptide proofreading, chaperones, mhc i, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 198558.84 |
| Authors | Domnick, A.,Susac, L.,Trowitzsch, S.,Thomas, C.,Tampe, R. (deposition date: 2022-01-03, release date: 2022-07-20, Last modification date: 2024-11-06) |
| Primary citation | Domnick, A.,Winter, C.,Susac, L.,Hennecke, L.,Hensen, M.,Zitzmann, N.,Trowitzsch, S.,Thomas, C.,Tampe, R. Molecular basis of MHC I quality control in the peptide loading complex. Nat Commun, 13:4701-4701, 2022 Cited by PubMed Abstract: Major histocompatibility complex class I (MHC I) molecules are central to adaptive immunity. Their assembly, epitope selection, and antigen presentation are controlled by the MHC I glycan through a sophisticated network of chaperones and modifying enzymes. However, the mechanistic integration of the corresponding processes remains poorly understood. Here, we determine the multi-chaperone-client interaction network of the peptide loading complex (PLC) and report the PLC editing module structure by cryogenic electron microscopy at 3.7 Å resolution. Combined with epitope-proofreading studies of the PLC in near-native lipid environment, these data show that peptide-receptive MHC I molecules are stabilized by multivalent chaperone interactions including the calreticulin-engulfed mono-glucosylated MHC I glycan, which only becomes accessible for processing by α-glucosidase II upon loading of optimal epitopes. Our work reveals allosteric coupling between peptide-MHC I assembly and glycan processing. This inter-process communication defines the onset of an adaptive immune response and provides a prototypical example of the tightly coordinated events in endoplasmic reticulum quality control. PubMed: 35948544DOI: 10.1038/s41467-022-32384-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.73 Å) |
Structure validation
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