Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4.
Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4.
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DOI：
10.1016/j.str.2010.04.017
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发表时间：
2010-08-11
期刊：
影响因子：
--
通讯作者：
Mer G
中科院分区：
文献类型：
--
作者：
Benirschke RC;Thompson JR;Nominé Y;Wasielewski E;Juranić N;Macura S;Hatakeyama S;Nakayama KI;Botuyan MV;Mer G
人E4 B，也称为UFD 2a，是一种含有U盒的蛋白质，其功能为E3泛素连接酶和E4聚泛素链延伸因子。E4 B被认为通过与伴侣蛋白结合参与错误折叠或受损蛋白的蛋白酶体降解。U-box结构域是E2泛素结合酶的锚位点，但对其结合机制知之甚少。使用X射线晶体学和NMR光谱，我们确定了E4 B U-box游离和结合UbcH 5c和Ubc 4 E2 s的结构。虽然以前的特点是U-盒域是同源二聚体，我们表明，E4 B的U-盒是一个单体稳定的氢键网络从标量耦合测量。这些结构的研究，补充量热法和NMR为基础的结合试验，建议UbcH 5c和Ubc 4的变构调节E4 B的U盒，并提供一个分子基础，了解如何泛素化机制，涉及E4 B组装。
Human E4B, also called UFD2a, is a U-box-containing protein that functions as an E3 ubiquitin ligase and an E4 polyubiquitin chain elongation factor. E4B is thought to participate in the proteasomal degradation of misfolded or damaged proteins through association with chaperones. The U-box domain is an anchor site for E2 ubiquitin-conjugating enzymes but little is known of the binding mechanism. Using X-ray crystallography and NMR spectroscopy, we determined the structures of E4B U-box free and bound to UbcH5c and Ubc4 E2s. While previously characterized U-box domains are homodimeric, we show that E4B U-box is a monomer stabilized by a network of hydrogen bonds identified from scalar coupling measurements. These structural studies, complemented by calorimetry- and NMR-based binding assays, suggest an allosteric regulation of UbcH5c and Ubc4 by E4B U-Box and provide a molecular basis to understand how the ubiquitylation machinery involving E4B assembles.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
64.5
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影响因子：
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作者：
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影响因子：
2.1
作者：
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通讯作者：
Nakayama, KI
影响因子：
2.7
作者：
Cordier, F;Dingley, AJ;Grzesiek, S
通讯作者：
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