7QPD

Structure of the human MHC I peptide-loading complex editing module

7QPD の概要

• エントリーDOI: 10.2210/pdb7qpd/pdb
• 関連するPDBエントリー: 6ENY
• EMDBエントリー: 14119
• 分子名称: Beta-2-microglobulin, Tapasin, Protein disulfide-isomerase A3, ... (7 entities in total)
• 機能のキーワード: antigen processing, peptide proofreading, chaperones, mhc i, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 198558.84

構造登録者

Domnick, A.,Susac, L.,Trowitzsch, S.,Thomas, C.,Tampe, R. (登録日: 2022-01-03, 公開日: 2022-07-20, 最終更新日: 2024-11-06)

主引用文献

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

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: 35948544
DOI: 10.1038/s41467-022-32384-z

実験手法

ELECTRON MICROSCOPY (3.73 Å)