5O6S

UbV.B4R, a dimeric ubiquitin variant binding to BIRC4 RING

5O6S の概要

• エントリーDOI: 10.2210/pdb5o6s/pdb
• 分子名称: Polyubiquitin-B (2 entities in total)
• 機能のキーワード: ubiquitin variant, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 55454.90

構造登録者

Gabrielsen, M.,Buetow, L.,Huang, D.T. (登録日: 2017-06-07, 公開日: 2017-11-01, 最終更新日: 2024-01-17)

主引用文献

Gabrielsen, M.,Buetow, L.,Nakasone, M.A.,Ahmed, S.F.,Sibbet, G.J.,Smith, B.O.,Zhang, W.,Sidhu, S.S.,Huang, D.T.
A General Strategy for Discovery of Inhibitors and Activators of RING and U-box E3 Ligases with Ubiquitin Variants.
Mol. Cell, 68:456-470.e10, 2017

PubMed Abstract: RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report the development of three ubiquitin variants (UbVs), each binding selectively to the RING or U-box domain of a distinct E3 ligase: monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and biochemical analyses revealed that UbVs specifically inhibited the activity of UBE4B or phosphorylated CBL by blocking the E2∼Ub binding site. Surprisingly, the UbV selective for dimeric XIAP formed a dimer to stimulate E3 activity by stabilizing the closed E2∼Ub conformation. We further verified the inhibitory and stimulatory functions of UbVs in cells. Our work provides a general strategy to inhibit or activate RING/U-box E3 ligases and provides a resource for the research community to modulate these enzymes.

PubMed: 29053960
DOI: 10.1016/j.molcel.2017.09.027

実験手法

X-RAY DIFFRACTION (2.9 Å)