4WLP

Crystal structure of UCH37-NFRKB Inhibited Deubiquitylating Complex

4WLP の概要

• エントリーDOI: 10.2210/pdb4wlp/pdb
• 関連するPDBエントリー: 4WLQ 4WLR
• 分子名称: Ubiquitin carboxyl-terminal hydrolase isozyme L5, Nuclear factor related to kappa-B-binding protein (2 entities in total)
• 機能のキーワード: uch37 nfrkb proteasome ino80 dub, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49954.56

構造登録者

Hemmis, C.W.,Hill, C.P.,VanderLinden, R.,Whitby, F.G. (登録日: 2014-10-07, 公開日: 2015-03-04, 最終更新日: 2023-12-27)

主引用文献

VanderLinden, R.T.,Hemmis, C.W.,Schmitt, B.,Ndoja, A.,Whitby, F.G.,Robinson, H.,Cohen, R.E.,Yao, T.,Hill, C.P.
Structural Basis for the Activation and Inhibition of the UCH37 Deubiquitylase.
Mol.Cell, 57:901-911, 2015

PubMed Abstract: The UCH37 deubiquitylase functions in two large and very different complexes, the 26S proteasome and the INO80 chromatin remodeler. We have performed biochemical characterization and determined crystal structures of UCH37 in complexes with RPN13 and NFRKB, which mediate its recruitment to the proteasome and INO80, respectively. RPN13 and NFRKB make similar contacts to the UCH37 C-terminal domain but quite different contacts to the catalytic UCH domain. RPN13 can activate UCH37 by disrupting dimerization, although physiologically relevant activation likely results from stabilization of a surface competent for ubiquitin binding and modulation of the active-site crossover loop. In contrast, NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. These findings reveal remarkable commonality in mechanisms of recruitment, yet very different mechanisms of regulating enzyme activity, and provide a foundation for understanding the roles of UCH37 in the unrelated proteasome and INO80 complexes.

PubMed: 25702872
DOI: 10.1016/j.molcel.2015.01.016

実験手法

X-RAY DIFFRACTION (3.102 Å)