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首页> 外文期刊>Journal of Molecular Biology >The N-terminal unstructured domain of yeast ODC functions as a transplantable and replaceable ubiquitin-independent degron.
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The N-terminal unstructured domain of yeast ODC functions as a transplantable and replaceable ubiquitin-independent degron.

机译：酵母ODC的N端非结构化结构域可作为可移植和可取代的遍在蛋白独立的degron。

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Ornithine decarboxylase (ODC), a homodimeric enzyme with a rate-limiting function in polyamine biosynthesis, is subject to a feedback control involving its selective proteolysis. Targeting of ODC monomers to the proteasome is mediated by ODC antizyme (OAZ), the expression of which is induced by high levels of polyamines. Here, we report our analysis of the N-terminal degron in Saccharomyces cerevisiae ODC and the mechanism of its antizyme-dependent targeting. This approximately 45-residue domain of ODC [termed ODC degradation signal (ODS)] is essential for degradation of ODC. Extensive mutagenesis indicated that it is not a specific sequence within ODS that is important but, rather, its unstructured nature. Consistent with this conclusion, ODS could be functionally replaced by an unrelated unstructured domain. We show that increasing the distance of ODS to the rest of the ODC protein reduced the dependence on Oaz1 for targeting, indicating that exposure of ODS is critical for its function. Disruption of ODC dimers by introducing interface mutations, in contrast, was insufficient for targeting. Binding of Oaz1 to ODC monomers is thus required to activate ODS. Fusion of ODS to the N terminus of Ura3 was sufficient to convert it into a ubiquitin-independent substrate of the proteasome. By contrast, ODS failed to destabilize maltose-binding protein or dihydrofolate reductase, indicating that this degron only operates in an appropriate structural context that enables rapid unfolding.
机译：鸟氨酸脱羧酶（ODC）是一种在聚胺生物合成中具有限速功能的同型二聚酶，受到涉及其选择性蛋白水解的反馈控制。将ODC单体靶向蛋白酶体是由ODC抗酶（OAZ）介导的，其表达是由高水平的多胺诱导的。在这里，我们报告我们在酿酒酵母ODC中的N末端地龙及其抗酶依赖性靶向机制的分析。 ODC的大约45个残基域[称为ODC降解信号（ODS）]对于ODC的降解至关重要。广泛的诱变表明，重要的不是ODS内的特定序列，而是其非结构化的性质。与该结论一致，ODS可以在功能上被不相关的非结构化域取代。我们显示，增加ODS与其余ODC蛋白的距离可降低对Oaz1的靶向依赖性，这表明ODS的暴露对其功能至关重要。相反，通过引入界面突变破坏ODC二聚体不足以靶向。因此需要Oaz1与ODC单体结合才能激活ODS。 ODS融合到Ura3的N末端足以将其转化为蛋白酶体的泛素依赖性底物。相比之下，ODS未能破坏麦芽糖结合蛋白或二氢叶酸还原酶的稳定性，表明该degron仅在能够快速展开的适当结构范围内运行。

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