9LE4

Crystal structure of the MIT-CD complex of STAMBP

9LE4 の概要

• エントリーDOI: 10.2210/pdb9le4/pdb
• 分子名称: STAM-binding protein, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ZINC ION, ... (5 entities in total)
• 機能のキーワード: stambp, deubiquitinase, autoinhibition, endocytosis
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 152035.80

構造登録者

Chen, Z.,Ding, J. (登録日: 2025-01-07, 公開日: 2025-06-11, 最終更新日: 2025-08-27)

主引用文献

Chen, Z.,Wang, G.,Zhang, Y.,Ding, J.
The MIT domain of STAMBP autoinhibits its deubiquitination activity.
Structure, 33:1337-, 2025

PubMed Abstract: STAMBP, a member of the JAMM family of deubiquitinases, specifically targets K63-linked polyubiquitin chains and plays a vital role in regulating the endosomal sorting of activated cell surface receptors. In this study, we conducted comprehensive biochemical analyses of full-length STAMBP and several fragments and demonstrated that the MIT domain binds tightly to the catalytic domain (CD), resulting in autoinhibition of its activity. The crystal structure of the MIT-CD complex reveals that the MIT domain occupies a large portion of the distal ubiquitin-binding site of the CD domain, thereby obstructing substrate binding. Additionally, our biochemical data show that STAM1 binding to STAMBP facilitates substrate binding and enhances its activity, whereas binding of CHMP3 does not relieve autoinhibition or enhance activity. In summary, our findings reveal an autoinhibition mechanism of STAMBP via its MIT domain and provide further insights into the relationships between STAMBP, STAM, and CHMP in regulating STAMBP's activity.

PubMed: 40441142
DOI: 10.1016/j.str.2025.05.001

実験手法

X-RAY DIFFRACTION (2.6 Å)