Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases.
Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases.
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DOI：
10.1016/j.jmb.2013.06.015
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发表时间：
2013-09-09
影响因子：
5.6
通讯作者：
Bullock, Alex N.
中科院分区：
文献类型：
--
作者：
Muniz, Joao R. C.;Guo, Kunde;Kershaw, Nadia J.;Ayinampudi, Vikram;von Delft, Frank;Babon, Jeffrey J.;Bullock, Alex N.
多亚基Cullin-RING E3连接酶通常使用重复结构域蛋白作为底物特异性衔接子。这些大分子组件的结构被确定为富含亮氨酸的F-盒重复序列和WD 40重复序列家族，但不为细胞因子信号传导抑制因子（SOCS）-盒锚蛋白重复序列蛋白（ASB 1 -18），它与延伸蛋白B和C和Cul 5组装。我们确定了ASB 9-Elongin B/C三元复合物以及Cul 5的相互作用N-末端结构域的晶体结构，并使用结构比较来建立完整的基于Cul 5的E3连接酶的模型。这些结构揭示了ASB 9复合物的独特结构，其将锚蛋白结构域定位为与SOCS盒-延伸蛋白B/C复合物同轴，并与其他重复蛋白复合物垂直。这种替代结构似乎有利于将锚蛋白结构域底物结合位点呈现给E2-遍在蛋白，同时还提供适合大体积ASB 9底物（例如肌酸激酶）的间隔。所提出的Cul 5结构也不同于以前的模型，并通过Cullin重复之间的刚体旋转偏离其他Cullin。这项工作突出了重复结构域蛋白作为底物识别支架的适应性，并为这个重要的E3家族的未来结构-功能研究奠定了基础。解析了ASB 9-延伸蛋白B/C复合物和相互作用Cul 5结构域的晶体结构。构建了它们组装成Cullin-RING E3连接酶的模型。这些含锚定蛋白的SOCS盒蛋白的分子结构偏离相关的F盒蛋白，以维持底物泛素化的精确几何结构。
Multi-subunit Cullin–RING E3 ligases often use repeat domain proteins as substrate-specific adaptors. Structures of these macromolecular assemblies are determined for the F-box-containing leucine-rich repeat and WD40 repeat families, but not for the suppressor of cytokine signaling (SOCS)-box-containing ankyrin repeat proteins (ASB1–18), which assemble with Elongins B and C and Cul5. We determined the crystal structures of the ternary complex of ASB9–Elongin B/C as well as the interacting N-terminal domain of Cul5 and used structural comparisons to establish a model for the complete Cul5-based E3 ligase. The structures reveal a distinct architecture of the ASB9 complex that positions the ankyrin domain coaxial to the SOCS box–Elongin B/C complex and perpendicular to other repeat protein complexes. This alternative architecture appears favorable to present the ankyrin domain substrate-binding site to the E2-ubiquitin, while also providing spacing suitable for bulky ASB9 substrates, such as the creatine kinases. The presented Cul5 structure also differs from previous models and deviates from other Cullins via a rigid-body rotation between Cullin repeats. This work highlights the adaptability of repeat domain proteins as scaffolds in substrate recognition and lays the foundation for future structure–function studies of this important E3 family. Crystal structures were solved for the ASB9–Elongin B/C complex and the interacting Cul5 domain. A model for their assembly into a Cullin–RING E3 ligase was constructed. The molecular architecture of these ankyrin-containing SOCS box proteins deviates from the related F-box proteins to maintain the precise geometry for substrate ubiquitylation.
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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：
Hao, B;Zheng, N;Pavletich, NP
通讯作者：
Pavletich, NP
DOI：
10.1073/pnas.0601638103
发表时间：
2006-05-16
影响因子：
11.1
作者：
Bullock, Alex N.;Debreczeni, Judit E.;Knapp, Stefan
通讯作者：
Knapp, Stefan
BIRC7-E2泛素结合结构揭示了环二聚体转移的泛素转移机制。
影响因子：
16.8
作者：
Dou, Hao;Buetow, Lori;Sibbet, Gary J.;Cameron, Kenneth;Huang, Danny T.
通讯作者：
Huang, Danny T.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH