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Title | Molecular basis of MHC I quality control in the peptide loading complex. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 4701, Year 2022 |
Publish date | Aug 10, 2022 |
![]() | Alexander Domnick / Christian Winter / Lukas Sušac / Leon Hennecke / Mario Hensen / Nicole Zitzmann / Simon Trowitzsch / Christoph Thomas / Robert Tampé / ![]() ![]() |
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 ...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. |
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Methods | EM (single particle) |
Resolution | 3.73 Å |
Structure data | EMDB-14119, PDB-7qpd: |
Source |
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![]() | IMMUNE SYSTEM / antigen processing / peptide proofreading / chaperones / MHC I |