Structural regulation of cullin-RING ubiquitin ligase complexes.
Structural regulation of cullin-RING ubiquitin ligase complexes.
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DOI：
10.1016/j.sbi.2011.01.003
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发表时间：
2011-04
影响因子：
6.8
通讯作者：
Schulman BA
中科院分区：
文献类型：
--
作者：
Duda DM;Scott DC;Calabrese MF;Zimmerman ES;Zheng N;Schulman BA
Cullin-RING 连接酶 (CRL) 构成最大的一类 E3 泛素连接酶。 CRL 是模块化多亚基酶，包含专用于特定 Cullin-RING 催化核心的可互换底物受体。最近的结构研究揭示了控制 CRL E3 连接酶活性的多种方式，包括通过共价连接泛素样蛋白 NEDD8 来激活多模式 E3 连接酶、通过 CAND1 抑制 CRL 组装/活性，以及调节底物募集的几种机制。这些特征凸显了 CRL 活性根据不同细胞信号进行调整的潜力，以及通过小分子激动剂或拮抗剂调节 CRL 功能的潜力。作为双篇评论系列的第二部分，本文重点关注最近的结构性研究，以增进我们对 CRL 活动如何监管的了解。
Cullin-RING ligases (CRLs) compose the largest class of E3 ubiquitin ligases. CRLs are modular, multisubunit enzymes, comprising interchangeable substrate receptors dedicated to particular Cullin-RING catalytic cores. Recent structural studies have revealed numerous ways in which CRL E3 ligase activities are controlled, including multimodal E3 ligase activation by covalent attachment of the ubiquitin-like protein NEDD8, inhibition of CRL assembly/activity by CAND1, and several mechanisms of regulated substrate recruitment. These features highlight the potential for CRL activities to be tuned in responses to diverse cellular cues, and for modulating CRL functions through small-molecule agonists or antagonists. As the second installment of a two-review series, this article focuses on recent structural studies advancing our knowledge of how CRL activities are regulated.