3UNE

Mouse constitutive 20S proteasome

3UNE の概要

• エントリーDOI: 10.2210/pdb3une/pdb
• 関連するPDBエントリー: 1IRU 1PMA 1RYP 3UN4 3UN8 3UNB 3UNF 3UNH
• 分子名称: Proteasome subunit alpha type-2, Proteasome subunit beta type-2, Proteasome subunit beta type-5, ... (15 entities in total)
• 機能のキーワード: 20s proteasome comprises 28 subunits, protease, cytosol, hydrolase
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Cytoplasm: P49722 Q9R1P3 O55234 O09061 Q60692 Q9R1P0 Q9Z2U0 Q9Z2U1 Q9R1P4 O70435 Q9QUM9 P70195 Q9R1P1; Cytoplasm (By similarity): P99026
• タンパク質・核酸の鎖数: 56
• 化学式量合計: 1435887.89

構造登録者

Huber, E.,Basler, M.,Schwab, R.,Heinemeyer, W.,Kirk, C.,Groettrup, M.,Groll, M. (登録日: 2011-11-15, 公開日: 2012-02-29, 最終更新日: 2024-11-20)

主引用文献

Huber, E.M.,Basler, M.,Schwab, R.,Heinemeyer, W.,Kirk, C.J.,Groettrup, M.,Groll, M.
Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity.
Cell(Cambridge,Mass.), 148:727-738, 2012

PubMed Abstract: Constitutive proteasomes and immunoproteasomes shape the peptide repertoire presented by major histocompatibility complex class I (MHC-I) molecules by harboring different sets of catalytically active subunits. Here, we present the crystal structures of constitutive proteasomes and immunoproteasomes from mouse in the presence and absence of the epoxyketone inhibitor PR-957 (ONX 0914) at 2.9 Å resolution. Based on our X-ray data, we propose a unique catalytic feature for the immunoproteasome subunit β5i/LMP7. Comparison of ligand-free and ligand-bound proteasomes reveals conformational changes in the S1 pocket of β5c/X but not β5i, thereby explaining the selectivity of PR-957 for β5i. Time-resolved structures of yeast proteasome:PR-957 complexes indicate that ligand docking to the active site occurs only via the reactive head group and the P1 side chain. Together, our results support structure-guided design of inhibitory lead structures selective for immunoproteasomes that are linked to cytokine production and diseases like cancer and autoimmune disorders.

PubMed: 22341445
DOI: 10.1016/j.cell.2011.12.030

実験手法

X-RAY DIFFRACTION (3.2 Å)