6QML

UCHL3 in complex with synthetic, K27-linked diubiquitin

6QML の概要

• エントリーDOI: 10.2210/pdb6qml/pdb
• 分子名称: Ubiquitin carboxyl-terminal hydrolase isozyme L3, Polyubiquitin-B, Polyubiquitin-C, ... (8 entities in total)
• 機能のキーワード: deubiquitinase inhibition, protein binding, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 87580.70

構造登録者

Murachelli, A.G.,Sixma, T.K. (登録日: 2019-02-07, 公開日: 2020-02-26, 最終更新日: 2024-10-23)

主引用文献

van Tilburg, G.B.A.,Murachelli, A.G.,Fish, A.,van der Heden van Noort, G.J.,Ovaa, H.,Sixma, T.K.
K27-Linked Diubiquitin Inhibits UCHL3 via an Unusual Kinetic Trap.
Cell Chem Biol, 28:191-201.e8, 2021

PubMed Abstract: Functional analysis of lysine 27-linked ubiquitin chains (Ub) is difficult due to the inability to make them through enzymatic methods and due to a lack of model tools and substrates. Here we generate a series of ubiquitin (Ub) tools to study how the deubiquitinase UCHL3 responds to Ub chains in comparison to lysine 63-linked chains and mono-Ub. From a crystal structure of a complex between UCHL3 and synthetic Ub, we unexpectedly discover that free Ub and Ub-conjugated substrates are natural inhibitors of UCHL3. Using our Ub tools to profile UCHL3's activity, we generate a quantitative kinetic model of the inhibitory mechanism and we find that Ub can inhibit UCHL3 covalently, by binding to its catalytic cysteine, and allosterically, by locking its catalytic loop tightly in place. Based on this inhibition mechanism, we propose that UCHL3 and Ub chains likely sense and regulate each other in cells.

PubMed: 33238157
DOI: 10.1016/j.chembiol.2020.11.005

実験手法

X-RAY DIFFRACTION (2.1 Å)