5CW6

Structure of metal dependent enzyme DrBRCC36

5CW6 の概要

• エントリーDOI: 10.2210/pdb5cw6/pdb
• 関連するPDBエントリー: 5CW3 5CW4 5CW5
• 分子名称: DrBRCC36, ZINC ION (3 entities in total)
• 機能のキーワード: metalloprotease, metal binding protein
• 由来する生物種: Danio rerio
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29845.63

構造登録者

Zeqiraj, E. (登録日: 2015-07-27, 公開日: 2015-09-16, 最終更新日: 2024-03-06)

主引用文献

Zeqiraj, E.,Tian, L.,Piggott, C.A.,Pillon, M.C.,Duffy, N.M.,Ceccarelli, D.F.,Keszei, A.F.,Lorenzen, K.,Kurinov, I.,Orlicky, S.,Gish, G.D.,Heck, A.J.,Guarne, A.,Greenberg, R.A.,Sicheri, F.
Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function.
Mol.Cell, 59:970-983, 2015

PubMed Abstract: BRCC36 is a Zn(2+)-dependent deubiquitinating enzyme (DUB) that hydrolyzes lysine-63-linked ubiquitin chains as part of distinct macromolecular complexes that participate in either interferon signaling or DNA-damage recognition. The MPN(+) domain protein BRCC36 associates with pseudo DUB MPN(-) proteins KIAA0157 or Abraxas, which are essential for BRCC36 enzymatic activity. To understand the basis for BRCC36 regulation, we have solved the structure of an active BRCC36-KIAA0157 heterodimer and an inactive BRCC36 homodimer. Structural and functional characterizations show how BRCC36 is switched to an active conformation by contacts with KIAA0157. Higher-order association of BRCC36 and KIAA0157 into a dimer of heterodimers (super dimers) was required for DUB activity and interaction with targeting proteins SHMT2 and RAP80. These data provide an explanation of how an inactive pseudo DUB allosterically activates a cognate DUB partner and implicates super dimerization as a new regulatory mechanism underlying BRCC36 DUB activity, subcellular localization, and biological function.

PubMed: 26344097
DOI: 10.1016/j.molcel.2015.07.028

実験手法

X-RAY DIFFRACTION (3.193 Å)