Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3.

Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3.
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DOI:
10.1038/nsmb.2621
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发表时间:
2013-08
影响因子:
16.8
通讯作者:
Huang, Danny T.
Huang, Danny T.
中科院分区:
生物学1区
文献类型:
--
作者:
Dou, Hao;Buetow, Lori;Sibbet, Gary J.;Cameron, Kenneth;Huang, Danny T.

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E3环连接酶催化泛素(Ub)从与Ub(E_2~Ub)硫酯化的E_2泛素结合酶转移到底物。对于环E3二聚体,一个亚基的环结构域和第二个亚基的尾部协同启动Ub,但在没有尾部成分的情况下,单体环E3如何实现这一点尚不清楚。在这里,我们提出了一个单体环E3,Tyr363-磷酸化的人CBL-B,与稳定的Ub连接的E2结合的晶体结构,揭示了激活E2~Ub的类似机制。PTyr363和pTyr363诱导的元件都直接与Ub的Ile36表面相互作用,使Ub转移的催化效率提高了约200倍。因此,正则环结构域外的相互作用对于优化单体和二聚环E3s中的Ub转移至关重要。我们认为,额外的非环Ub启动元件可能是常见的环E3特征。
RING E3 ligases catalyze the transfer of ubiquitin (Ub) from E2 ubiquitin-conjugating enzyme thioesterified with Ub (E2~Ub) to substrate. For RING E3 dimers, the RING domain of one subunit and tail of the second cooperate to prime Ub, but how this is accomplished by monomeric RING E3s in the absence of a tail-like component is unknown. Here, we present a crystal structure of a monomeric RING E3, Tyr363-phosphorylated human CBL-B, bound to a stabilized Ub-linked E2, revealing a similar mechanism in activating E2~Ub. Both pTyr363 and the pTyr363-induced element interact directly with Ub’s Ile36 surface, improving the catalytic efficiency of Ub transfer by ~200-fold. Hence, interactions outside the canonical RING domain are crucial for optimizing Ub transfer in both monomeric and dimeric RING E3s. We propose that an additional non-RING Ub-priming element may be a common RING E3 feature.
DOI: 10.1038/nsmb.2108
发表时间: 2011-08-21
影响因子: 16.8
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