9QB1

Yeast 20S proteasome mutant: beta5_T3M in complex with Bortezomib

これはPDB形式変換不可エントリーです。

9QB1 の概要

• エントリーDOI: 10.2210/pdb9qb1/pdb
• 関連するPDBエントリー: 5CZ4
• 分子名称: Proteasome subunit alpha type-2, Proteasome subunit beta type-4, Proteasome subunit beta type-5, ... (18 entities in total)
• 機能のキーワード: proteasome, proteasome associated autoinflammatory syndromes, mutation, assembly, maturation, hydrolase
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast); 詳細
• タンパク質・核酸の鎖数: 34
• 化学式量合計: 733503.48

構造登録者

Huber, E.M.,Heinemeyer, W.,Groll, M. (登録日: 2025-02-28, 公開日: 2025-10-08, 最終更新日: 2025-12-17)

主引用文献

Huber, E.M.,Heinemeyer, W.,Groll, M.
Proteasome-associated autoinflammatory syndromes: The impact of mutations in proteasome subunits on particle assembly, structure, and activity.
Structure, 33:2084-, 2025

PubMed Abstract: Single point mutations in proteasome subunits can cause severe autoinflammatory syndromes. By still largely unknown mechanisms, some of these disease-associated mutations impair normal proteasome function and induce the production of pro-inflammatory cytokines, thereby leading to systemic inflammations. In order to obtain more insights on why and how the mutations T3M and G128V in the immunoproteasome subunit β5i trigger such deleterious effects, we created the respective yeast mutants and characterized their phenotypes with special emphasis on proteasome structure and activity. X-ray crystallographic data revealed that the mutation T3M influences structure and flexibility of the proteasomal substrate-binding channel with moderate impairment of proteasome biogenesis, whereas the amino acid substitution G128V causes larger structural rearrangements that severely disturb particle assembly and maturation. The obtained results provide a deeper understanding of how single point mutations can affect proteasome subunit structure as well as particle biogenesis and ultimately cause chronic inflammatory diseases.

PubMed: 41033310
DOI: 10.1016/j.str.2025.09.004

実験手法

X-RAY DIFFRACTION (2.8 Å)