Department of Cell and Molecular Biology, Karolinska Institutet, von Eulers väg 3, S-17177 Stockholm, Sweden.
Nat Commun. 2011 Feb 8;2:191. doi: 10.1038/ncomms1179.
The ubiquitin receptors Rad23 and Dsk2 deliver polyubiquitylated substrates to the proteasome for destruction. The C-terminal ubiquitin-associated (UBA) domain of Rad23 functions as a cis-acting stabilization signal that protects this protein from proteasomal degradation. Here, we provide evidence that the C-terminal UBA domains guard ubiquitin receptors from destruction by preventing initiation of degradation at the proteasome. We show that introduction of unstructured polypeptides that are sufficiently long to function as initiation sites for degradation abrogates the protective effect of UBA domains. Vice versa, degradation of substrates that contain an unstructured extension can be attenuated by the introduction of C-terminal UBA domains. Our study gains insight into the molecular mechanism responsible for the protective effect of UBA domains and explains how ubiquitin receptors can shuttle substrates to the proteasome without themselves becoming subject to proteasomal degradation.
泛素受体 Rad23 和 Dsk2 将多泛素化的底物递送至蛋白酶体进行降解。Rad23 的 C 端泛素相关 (UBA) 结构域作为一个顺式作用的稳定信号，保护该蛋白免受蛋白酶体降解。在这里，我们提供的证据表明，C 端 UBA 结构域通过防止在蛋白酶体处开始降解来保护泛素受体免受破坏。我们表明，引入足够长的无规卷曲多肽作为降解起始位点会破坏 UBA 结构域的保护作用。相反，通过引入 C 端 UBA 结构域可以减弱含有无规卷曲延伸的底物的降解。我们的研究深入了解了 UBA 结构域保护作用的分子机制，并解释了泛素受体如何在不自身被蛋白酶体降解的情况下将底物穿梭到蛋白酶体。
