Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4.

Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4.
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DOI:
10.1038/ncomms5217
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发表时间:
2014-06-27
影响因子:
16.6
通讯作者:
Matthews, Steve J.
Matthews, Steve J.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Xu, Yingqi;Plechanovova, Anna;Simpson, Peter;Marchant, Jan;Leidecker, Orsolya;Kraatz, Sebastian;Hay, Ronald T.;Matthews, Steve J.

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小泛素样修饰物(SUMO)可以形成聚合链,这些聚合链是细胞过程中的重要信号,如减数分裂,基因组维持和应激反应。SUMO靶向泛素连接酶RNF4与连接底物上的SUMO链接合并催化其泛素化,其靶向蛋白酶体降解的底物。在这里,我们使用一个节段标记的方法结合溶液核磁共振(NMR)光谱和生化表征,以揭示如何RNF4操纵的SUMO链的构象,从而促进泛素转移的远端SUMO结构域的最佳交付。 SUMO形成可与泛素连接酶(如RNF4)相互作用的柔性聚合链。Xu等人使用NMR光谱和生物化学实验来研究SUMO和RNF4之间的相互作用,并提出了将底物传递到泛素化机制的机制。
The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 engages with SUMO chains on linked substrates and catalyses their ubiquitination, which targets substrates for proteasomal degradation. Here we use a segmental labelling approach combined with solution nuclear magnetic resonance (NMR) spectroscopy and biochemical characterization to reveal how RNF4 manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer. SUMO forms flexible polymeric chains that can interact with ubiquitin ligases, such as RNF4. Here Xu et al. have used NMR spectroscopy and biochemical experiments to investigate the interaction between SUMO and RNF4, and propose a mechanism for delivery of substrates to the ubiquitination machinery.
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发表时间: 1998-04-01
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