4X5X

HLA-DR1 mutant bN82A with covalently linked CLIP106-120(M107W)

4X5X の概要

• エントリーDOI: 10.2210/pdb4x5x/pdb
• 分子名称: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1-1 beta chain (2 entities in total)
• 機能のキーワード: mhc ii, immune system, self antigen, invariant chain, clip
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P01903 P04229
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 96230.23

構造登録者

Guenther, S.,Freund, C. (登録日: 2014-12-06, 公開日: 2016-03-09, 最終更新日: 2024-10-16)

主引用文献

Wieczorek, M.,Sticht, J.,Stolzenberg, S.,Gunther, S.,Wehmeyer, C.,El Habre, Z.,Alvaro-Benito, M.,Noe, F.,Freund, C.
MHC class II complexes sample intermediate states along the peptide exchange pathway.
Nat Commun, 7:13224-13224, 2016

PubMed Abstract: The presentation of peptide-MHCII complexes (pMHCIIs) for surveillance by T cells is a well-known immunological concept in vertebrates, yet the conformational dynamics of antigen exchange remain elusive. By combining NMR-detected H/D exchange with Markov modelling analysis of an aggregate of 275 microseconds molecular dynamics simulations, we reveal that a stable pMHCII spontaneously samples intermediate conformations relevant for peptide exchange. More specifically, we observe two major peptide exchange pathways: the kinetic stability of a pMHCII's ground state defines its propensity for intrinsic peptide exchange, while the population of a rare, intermediate conformation correlates with the propensity of the HLA-DM-catalysed pathway. Helix-destabilizing mutants designed based on our model shift the exchange behaviour towards the HLA-DM-catalysed pathway and further allow us to conceptualize how allelic variation can shape an individual's MHC restricted immune response.

PubMed: 27827392
DOI: 10.1038/ncomms13224

実験手法

X-RAY DIFFRACTION (3.199 Å)