Allosteric activation of E2-RING finger-mediated ubiquitylation by a structurally defined specific E2-binding region of gp78.
Allosteric activation of E2-RING finger-mediated ubiquitylation by a structurally defined specific E2-binding region of gp78.
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DOI：
10.1016/j.molcel.2009.05.010
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发表时间：
2009-06-26
期刊：
影响因子：
16
通讯作者：
Weissman, Allan M.
中科院分区：
文献类型：
--
作者：
Das, Ranabir;Mariano, Jennifer;Tsai, Yien Che;Kalathur, Ravi C.;Kostova, Zlatka;Li, Jess;Tarasov, Sergey G.;McFeeters, Robert L.;Altieri, Amanda S.;Ji, Xinhua;Byrd, R. Andrew;Weissman, Allan M.
RING指泛素连接酶（E3）的活性取决于它们促进泛素从泛素缀合酶（E2）转移到底物的能力。E3 gp 78内的G2 BR结构域选择性地并以高亲和力结合E2 Ube 2g 2。通过结构和功能分析，我们确定这发生在Ube 2g 2的一个区域，不同于泛素激活酶（E1）和RING指的结合位点。与G2 BR的结合导致Ube 2g 2的构象变化，从而影响泛素负载。Ube 2g 2：G2 BR相互作用还导致E2和RING指之间的亲和力增加约50倍。这导致Ube 2g 2和gp 78 RING指的泛素化显著增加。当Ube 2g 2与其他RING指E3配对时，观察到的泛素化增强强调了G2 BR效应的重要性。这些发现揭示了E2的变构效应增强E2-RING指相互作用并因此增强遍在化的机制。
The activity of RING finger ubiquitin ligases (E3) is dependent on their ability to facilitate transfer of ubiquitin from ubiquitin-conjugating enzymes (E2) to substrates. The G2BR domain within the E3 gp78 binds selectively and with high affinity to the E2 Ube2g2. Through structural and functional analyses, we determine that this occurs on a region of Ube2g2 distinct from binding sites for ubiquitin-activating enzyme (E1) and RING fingers. Binding to the G2BR results in conformational changes in Ube2g2 that affect ubiquitin loading. The Ube2g2:G2BR interaction also causes an ~ 50-fold increase in affinity between the E2 and RING finger. This results in markedly increased ubiquitylation by Ube2g2 and the gp78 RING finger. The significance of this G2BR effect is underscored by enhanced ubiquitylation observed when Ube2g2 is paired with other RING finger E3s. These findings uncover a mechanism whereby allosteric effects on an E2 enhance E2-RING finger interactions and consequently ubiquitylation.
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