UBL/UBA ubiquitin receptor proteins bind a common tetraubiquitin chain
UBL/UBA ubiquitin receptor proteins bind a common tetraubiquitin chain
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DOI：
10.1016/j.jmb.2005.12.001
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发表时间：
2006-03-03
影响因子：
5.6
通讯作者：
Walters, KJ
中科院分区：
文献类型：
--
作者：
Kang, Y;Vossler, RA;Walters, KJ
泛素-蛋白酶体途径在细胞的整个生命周期中是必不可少的。该系统使用数量惊人的蛋白质进行泛素化，并将蛋白质底物传递给蛋白酶体进行降解。这个过程的核心是一个庞大且不断增长的泛素受体蛋白家族。在这个家族中，有一个被广泛研究的群体，包含泛素样（UBL）和泛素相关（UBA）结构域：Rad23， Ddi1和Dsk2。尽管有报道称UBL/UBA家族成员调节其他蛋白质的降解，但由于它们的功能角色重叠，相互作用以及与其他泛素家族成员的相互作用，它们在泛素介导的蛋白质降解中的个体作用已被证明难以解决。在这里，我们使用核磁共振波谱和分子生物学相结合的方法揭示了Rad23和Ddi1通过UBL/UBA结构域相互作用相互作用，这种相互作用并不妨碍它们与泛素的相互作用。我们证明了UBL/UBA蛋白可以结合一个常见的四红素分子，从而为链采用开放结构结合多个受体蛋白的模型提供了强有力的证据。总之，我们的研究结果表明，通过这种机制，UBL/UBA蛋白可以保护链在转运到蛋白酶体时免受过早的去泛素化和不必要的延伸。(c) 2005 Elsevier Ltd版权所有。
The ubiquitin-proteasome pathway is essential throughout the life cycle of a cell. This system employs an astounding number of proteins to ubiquitylate and to deliver protein substrates to the proteasome for their degradation. At the heart of this process is the large and growing family of ubiquitin receptor proteins. Within this family is an intensely studied group that contains both ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains: Rad23, Ddi1 and Dsk2. Although UBL/UBA family members are reported to regulate the degradation of other proteins, their individual roles in ubiquitin-mediated protein degradation has proven difficult to resolve due to their overlapping functional roles and interaction with each other and other ubiquitin family members. Here, we use a combination of NMR spectroscopy and molecular biology to reveal that Rad23 and Ddi1 interact with each other by using UBL/UBA domain interactions in a manner that does not preclude their interaction with ubiquitin. We demonstrate that UBL/UBA proteins can bind a common tetraubiquitin molecule and thereby provide strong evidence for a model in which chains adopt an opened structure to bind multiple receptor proteins. Altogether our results suggest a mechanism through which UBL/UBA proteins could protect chains from premature de-ubiquitylation and unnecessary elongation during their transit to the proteasome. (c) 2005 Elsevier Ltd. All rights reserved.