5KSU

Crystal structure of HLA-DQ2.5-CLIP1 at 2.73 resolution

5KSU の概要

• エントリーDOI: 10.2210/pdb5ksu/pdb
• 関連するPDBエントリー: 5KSV
• 分子名称: HLA class II histocompatibility antigen, DQ alpha 1 chain, MHC class II HLA-DQ-beta-1, HLA class II histocompatibility antigen gamma chain, ... (4 entities in total)
• 機能のキーワード: hla, mhc, dq2.5, clip, celiac disease, immune system
• 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: P01909
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 95767.97

構造登録者

Nguyen, T.-B.,Jayaraman, P.,Bergseng, E.,Madhusudhan, M.S.,Kim, C.-Y.,Sollid, L.M. (登録日: 2016-07-10, 公開日: 2017-04-05, 最終更新日: 2024-10-23)

主引用文献

Nguyen, T.B.,Jayaraman, P.,Bergseng, E.,Madhusudhan, M.S.,Kim, C.Y.,Sollid, L.M.
Unraveling the structural basis for the unusually rich association of human leukocyte antigen DQ2.5 with class-II-associated invariant chain peptides.
J. Biol. Chem., 292:9218-9228, 2017

PubMed Abstract: Human leukocyte antigen (HLA)-DQ2.5 (**) is a class-II major histocompatibility complex protein associated with both type 1 diabetes and celiac disease. One unusual feature of DQ2.5 is its high class-II-associated invariant chain peptide (CLIP) content. Moreover, HLA-DQ2.5 preferentially binds the non-canonical CLIP2 over the canonical CLIP1. To better understand the structural basis of HLA-DQ2.5's unusual CLIP association characteristics, better insight into the HLA-DQ2.5·CLIP complex structures is required. To this end, we determined the X-ray crystal structure of the HLA-DQ2.5· CLIP1 and HLA-DQ2.5·CLIP2 complexes at 2.73 and 2.20 Å, respectively. We found that HLA-DQ2.5 has an unusually large P4 pocket and a positively charged peptide-binding groove that together promote preferential binding of CLIP2 over CLIP1. An α9-α22-α24-α31-β86-β90 hydrogen bond network located at the bottom of the peptide-binding groove, spanning from the P1 to P4 pockets, renders the residues in this region relatively immobile. This hydrogen bond network, along with a deletion mutation at α53, may lead to HLA-DM insensitivity in HLA-DQ2.5. A molecular dynamics simulation experiment reported here and recent biochemical studies by others support this hypothesis. The diminished HLA-DM sensitivity is the likely reason for the CLIP-rich phenotype of HLA-DQ2.5.

PubMed: 28364043
DOI: 10.1074/jbc.M117.785139

実験手法

X-RAY DIFFRACTION (2.73 Å)