7X1B

Crystal structure of peptide KAGQVVTI in complex with HLA-B5801

7X1B の概要

• エントリーDOI: 10.2210/pdb7x1b/pdb
• 分子名称: HLA-B, Beta-2-microglobulin, LYS-ALA-GLY-GLN-VAL-VAL-THR-ILE, ... (5 entities in total)
• 機能のキーワード: immune system, human leukocyte antigen
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44749.67

構造登録者

Huan, X.,Ren, E.C. (登録日: 2022-02-23, 公開日: 2023-05-03, 最終更新日: 2024-10-23)

主引用文献

Huan, X.,Zhuo, N.,Lee, H.Y.,Ren, E.C.
Allopurinol non-covalently facilitates binding of unconventional peptides to HLA-B*58:01.
Sci Rep, 13:9373-9373, 2023

PubMed Abstract: Allopurinol, widely used in gout treatment, is the most common cause of severe cutaneous adverse drug reactions. The risk of developing such life-threatening reactions is increased particularly for HLA-B*58:01 positive individuals. However the mechanism of action between allopurinol and HLA remains unknown. We demonstrate here that a Lamin A/C peptide KAGQVVTI which is unable to bind HLA-B*58:01 on its own, is enabled to form a stable peptide-HLA complex only in the presence of allopurinol. Crystal structure analysis reveal that allopurinol non-covalently facilitated KAGQVVTI to adopt an unusual binding conformation, whereby the C-terminal isoleucine does not engage as a PΩ that typically fit deeply in the binding F-pocket. A similar observation, though to a lesser degree was seen with oxypurinol. Presentation of unconventional peptides by HLA-B*58:01 aided by allopurinol contributes to our fundamental understanding of drug-HLA interactions. The binding of peptides from endogenously available proteins such as self-protein lamin A/C and viral protein EBNA3B suggest that aberrant loading of unconventional peptides in the presence of allopurinol or oxypurinol may be able to trigger anti-self reactions that can lead to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

PubMed: 37296297
DOI: 10.1038/s41598-023-36293-z

実験手法

X-RAY DIFFRACTION (1.399 Å)