Co-adaptor driven assembly of a CUL3 E3 ligase complex.
Co-adaptor driven assembly of a CUL3 E3 ligase complex.
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DOI：
10.1016/j.molcel.2022.01.004
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发表时间：
2022-02-03
期刊：
影响因子：
16
通讯作者：
Rapé M
中科院分区：
文献类型：
--
作者：
Akopian D;McGourty CA;Rapé M
库林环状E3连接酶(CRL)是一种必需的泛素化酶，它将围绕在库林支架周围的催化核心与~300个可交换的底物接头结合在一起。为了确保强大的信号转导，细胞必须不断地通过将底物结合的适配器与它们的库林配对来形成新的CRL，但这是如何在正确的时间和地点发生的仍然知之甚少。在这里，我们证明了单个CRL复合体的形成是一个严格调控的过程。以CUL3KLHL12为模型，我们发现其共接头PEF1-ALG2通过从内质网的组装抑制剂释放KLHL12来启动CRL3的形成，然后协同接头单素基化稳定酶以进行底物修饰。由于辅适配子也有助于招募底物，它在CRL组装中的作用将靶标识别与泛素化结合起来。我们建议专用于特定CRL的调节因子，如组装抑制剂或共适配子，与靶标无关的适配器交换机制合作，建立控制后生动物发育的E3连接酶复合体。模块化的E3连接酶对于信号转导是必不可少的，但细胞如何控制它们的组成还不完全清楚。作为对一般接头交换机制的补充，作者指出，CUL3 E3连接酶的形成需要适时地从组装抑制剂中释放可交换的接头，并通过可逆单糖苷化来实现络合物的稳定。
Cullin-RING E3 ligases (CRLs) are essential ubiquitylation enzymes that combine a catalytic core built around cullin scaffolds with ~300 exchangeable substrate adaptors. To ensure robust signal transduction, cells must constantly form new CRLs by pairing substrate-bound adaptors with their cullins, but how this occurs at the right time and place is still poorly understood. Here, we show that formation of individual CRL complexes is a tightly regulated process. Using CUL3KLHL12 as a model, we found that its co-adaptor PEF1-ALG2 initiates CRL3 formation by releasing KLHL12 from an assembly inhibitor at the endoplasmic reticulum, before co-adaptor monoubiquitylation stabilizes the enzyme for substrate modification. As the co-adaptor also helps recruit substrates, its role in CRL assembly couples target recognition to ubiquitylation. We propose that regulators dedicated to specific CRLs, such as assembly inhibitors or co-adaptors, cooperate with target-agnostic adaptor exchange mechanisms to establish E3 ligase complexes that control metazoan development. Modular E3 ligases are essential for signal transduction, but how cells control their composition is not fully understood. Complementing general adaptor exchange mechanisms, the authors show that formation of a CUL3 E3 ligase requires timely release of an exchangeable adaptor from an assembly inhibitor and complex stabilization through reversible monoubiquitylation.
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DOI：
10.1074/jbc.m112.352484
发表时间：
2012-08-24
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Emberley ED;Mosadeghi R;Deshaies RJ
通讯作者：
Deshaies RJ
DOI：
10.1073/pnas.1423026112
发表时间：
2015-01-13
影响因子：
11.1
作者：
Chen, Shuliang;Desai, Tanvi;Novick, Peter J.
通讯作者：
Novick, Peter J.
影响因子：
5.8
作者：
Chen, Zhuoyao;Wasney, Gregory A.;Bullock, Alex N.
通讯作者：
Bullock, Alex N.
影响因子：
64.8
作者：
Huttlin EL;Bruckner RJ;Paulo JA;Cannon JR;Ting L;Baltier K;Colby G;Gebreab F;Gygi MP;Parzen H;Szpyt J;Tam S;Zarraga G;Pontano-Vaites L;Swarup S;White AE;Schweppe DK;Rad R;Erickson BK;Obar RA;Guruharsha KG;Li K;Artavanis-Tsakonas S;Gygi SP;Harper JW
通讯作者：
Harper JW
影响因子：
64.5
作者：
Huttlin EL;Ting L;Bruckner RJ;Gebreab F;Gygi MP;Szpyt J;Tam S;Zarraga G;Colby G;Baltier K;Dong R;Guarani V;Vaites LP;Ordureau A;Rad R;Erickson BK;Wühr M;Chick J;Zhai B;Kolippakkam D;Mintseris J;Obar RA;Harris T;Artavanis-Tsakonas S;Sowa ME;De Camilli P;Paulo JA;Harper JW;Gygi SP
通讯作者：
Gygi SP