The Yeast E4 Ubiquitin Ligase Ufd2 Interacts with the Ubiquitin-like Domains of Rad23 and Dsk2 via a Novel and Distinct Ubiquitin-like Binding Domain
The Yeast E4 Ubiquitin Ligase Ufd2 Interacts with the Ubiquitin-like Domains of Rad23 and Dsk2 via a Novel and Distinct Ubiquitin-like Binding Domain
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DOI：
10.1074/jbc.m110.112532
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发表时间：
2010-06-25
影响因子：
4.8
通讯作者：
Raasi, Shahri
中科院分区：
文献类型：
--
作者：
Haenzelmann, Petra;Stingele, Julian;Raasi, Shahri
含有泛素样（UBL）和泛素相关（乌巴）结构域的蛋白质与各种结合伴侣相互作用，并在泛素介导的蛋白质降解过程中起枢纽作用。芽殖酵母UBL-UBA蛋白Rad 23和Dsk 2与E4泛素连接酶Ufd 2的共同相互作用已在内质网相关降解等途径中描述。Rad 23和Dsk 2的UBL结构域通过与Ufd 2和26 S蛋白酶体的不同亚基相互作用在该过程中发挥重要作用。在这里，我们报告的晶体结构的Ufd 2在复杂的UBL域的Rad 23和Dsk 2。Ufd 2的N-末端UBL相互作用区域呈现出独特的序列模式，这与迄今为止鉴定的任何已知的泛素或UBL结合结构域不同。残基特异性差异存在于这些UBL结构域与Ufd 2的相互作用中，这与它们的结合亲和力的细微差异相结合。它们之间差异相互作用的分子细节表明了适应性进化在塑造这些界面中的作用。
Proteins containing ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains interact with various binding partners and function as hubs during ubiquitin-mediated protein degradation. A common interaction of the budding yeast UBL-UBA proteins Rad23 and Dsk2 with the E4 ubiquitin ligase Ufd2 has been described in endoplasmic reticulum-associated degradation among other pathways. The UBL domains of Rad23 and Dsk2 play a prominent role in this process by interacting with Ufd2 and different subunits of the 26 S proteasome. Here, we report crystal structures of Ufd2 in complex with the UBL domains of Rad23 and Dsk2. The N-terminal UBL-interacting region of Ufd2 exhibits a unique sequence pattern, which is distinct from any known ubiquitin-or UBL-binding domain identified so far. Residue-specific differences exist in the interactions of these UBL domains with Ufd2, which are coupled to subtle differences in their binding affinities. The molecular details of their differential interactions point to a role for adaptive evolution in shaping these interfaces.