TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes.
TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes.
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DOI：
10.1038/emboj.2013.209
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发表时间：
2013-10-30
期刊：
影响因子：
11.4
通讯作者：
Alpi, Arno F.
中科院分区：
文献类型：
--
作者：
Kelsall, Ian R.;Duda, David M.;Olszewski, Jennifer L.;Hofmann, Kay;Knebel, Axel;Langevin, Frederic;Wood, Nicola;Wightman, Melanie;Schulman, Brenda A.;Alpi, Arno F.
RING (Really Interesting New Gene)-in-between-RING （RBR）酶是一类独特的E3泛素连接酶，具有三个锌结合结构域，协同催化泛素转移。大多数RBR连接酶成员的调控和生物学功能尚不清楚，迄今为止表征的所有RBR E3s在体外泛素化过程中都被自动抑制。在这里，我们发现TRIAD1和hari， Ariadne亚家族的两个成员，与不同的类木化Cullin-RING连接酶（CRL）复合物相关联。与分离的TRIAD1或hari显示的适度E3连接酶活性相比，同源的类木化CRL与TRIAD1或hari的结合极大地刺激了体外RBR连接酶的活性，这是通过自泛素化确定的，它们能够刺激硫酯连接的UBCH7 -泛素中间体的解离，以及与泛素-乙烯基甲酯的反应性。此外，遗传证据表明，RBR连接酶活性影响体内类木化修饰的crl的水平和活性。总的来说，我们的工作提出了crl诱导Ariadne RBR连接酶激活的保守机制，并进一步表明这类特殊的RBR作为不同crl的调节因子具有互惠作用。
RING (Really Interesting New Gene)-in-between-RING (RBR) enzymes are a distinct class of E3 ubiquitin ligases possessing a cluster of three zinc-binding domains that cooperate to catalyse ubiquitin transfer. The regulation and biological function for most members of the RBR ligases is not known, and all RBR E3s characterized to date are auto-inhibited for in vitro ubiquitylation. Here, we show that TRIAD1 and HHARI, two members of the Ariadne subfamily ligases, associate with distinct neddylated Cullin-RING ligase (CRL) complexes. In comparison to the modest E3 ligase activity displayed by isolated TRIAD1 or HHARI, binding of the cognate neddylated CRL to TRIAD1 or HHARI greatly stimulates RBR ligase activity in vitro, as determined by auto-ubiquitylation, their ability to stimulate dissociation of a thioester-linked UBCH7∼ubiquitin intermediate, and reactivity with ubiquitin-vinyl methyl ester. Moreover, genetic evidence shows that RBR ligase activity impacts both the levels and activities of neddylated CRLs in vivo. Cumulatively, our work proposes a conserved mechanism of CRL-induced Ariadne RBR ligase activation and further suggests a reciprocal role of this special class of RBRs as regulators of distinct CRLs.
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影响因子：
64.5
作者：
Duda, David M.;Borg, Laura A.;Scott, Daniel C.;Hunt, Harold W.;Hammel, Michal;Schulman, Brenda A.
通讯作者：
Schulman, Brenda A.
影响因子：
16
作者：
Kurz, Thimo;Chou, Yang-Chieh;Sicheri, Frank
通讯作者：
Sicheri, Frank
环手指（RBR）蛋白质家族之间的环。
影响因子：
12.3
作者：
Eisenhaber B;Chumak N;Eisenhaber F;Hauser MT
通讯作者：
Hauser MT
影响因子：
6.8
作者：
Duda DM;Scott DC;Calabrese MF;Zimmerman ES;Zheng N;Schulman BA
通讯作者：
Schulman BA
影响因子：
16
作者：
Huang, Danny T.;Ayrault, Olivier;Hunt, Harold W.;Taherbhoy, Asad M.;Duda, David M.;Scott, Daniel C.;Borg, Laura A.;Neale, Geoffrey;Murray, Peter J.;Roussel, Martine F.;Schulman, Brenda A.
通讯作者：
Schulman, Brenda A.