Quality Control of a Cytoplasmic Protein Complex
Quality Control of a Cytoplasmic Protein Complex
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DOI：
10.1074/jbc.m114.596064
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发表时间：
2015-01
期刊：
影响因子：
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通讯作者：
Mario Scazzari;Ingo Amm;D. Wolf
中科院分区：
文献类型：
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作者：
Mario Scazzari;Ingo Amm;D. Wolf
背景：蛋白质复合体中多余的亚基被降解，以避免不必要的错误反应。结果：由HSP70、CDC48和泛素-蛋白酶体系统的组件组成的机械消除了孤儿脂肪酸合成酶亚单位Fas2。结论：伴侣马达和泛素-蛋白酶体系统平衡脂肪酸合成酶复合体的动态平衡。意义：选择性蛋白分解是调节蛋白质复合体化学计量学的一种工具。对于蛋白质复合体在细胞中的组装，化学计量的各个蛋白质亚基的存在是至关重要的。任何亚基的过剩都可能引发非特异性和有害的蛋白质相互作用，必须避免。最终必须通过转录、翻译和/或翻译后调控达到化学计量的亚基数量。饱和的16和18碳脂肪酸的合成是由脂肪酸合成酶完成的：在酿酒酵母中，一个2，6-丙二醛的分子质量组合，包含6个Protomer，每个都有两个不同的亚基，Fas1(β)和Fas2(α)。(α)6(β)6复合体携带脂肪酸合成所需的全部8种酶活性的6个副本。酵母中的FAS1和FAS2基因是不连锁的，并定位在两条不同的染色体上。在这里，我们研究了当其伴侣α亚基Fas 1缺失时，复合体的β亚基Fas 2的命运。当各自的伴侣缺失时，脂肪酸合成酶的各个亚基就会被蛋白质降解。Fas2的消除是通过蛋白酶体实现的。我们在这里展示了消除Fas2所需要的泛素转移机制。针对蛋白酶体中多余的Fas2亚基的主要泛素连接酶是Ubr1。泛素结合酶Ubc2和Ubc4协助降解过程。AAA-ATPase CDC48和Hsp70分子伴侣Ssa1在Fas2的消除中起着至关重要的作用。
Background: Superfluous subunits of protein complexes are degraded to avoid unwanted erroneous reactions. Results: A machinery consisting of Hsp70, Cdc48, and components of the ubiquitin-proteasome system eliminates orphan fatty acid synthase subunit Fas2. Conclusion: Chaperone motors and the ubiquitin-proteasome system balance the homeostasis of the fatty acid synthase complex. Significance: Selective proteolysis is a tool to regulate protein complex stoichiometry. For the assembly of protein complexes in the cell, the presence of stoichiometric amounts of the respective protein subunits is of utmost importance. A surplus of any of the subunits may trigger unspecific and harmful protein interactions and has to be avoided. A stoichiometric amount of subunits must finally be reached via transcriptional, translational, and/or post-translational regulation. Synthesis of saturated 16 and 18 carbon fatty acids is carried out by fatty acid synthase: in yeast Saccharomyces cerevisiae, a 2.6-MDa molecular mass assembly containing six protomers each of two different subunits, Fas1 (β) and Fas2 (α). The (α)6(β)6 complex carries six copies of all eight enzymatic activities required for fatty acid synthesis. The FAS1 and FAS2 genes in yeast are unlinked and map on two different chromosomes. Here we study the fate of the α-subunit of the complex, Fas2, when its partner, the β-subunit Fas1, is absent. Individual subunits of fatty acid synthase are proteolytically degraded when the respective partner is missing. Elimination of Fas2 is achieved by the proteasome. Here we show that a ubiquitin transfer machinery is required for Fas2 elimination. The major ubiquitin ligase targeting the superfluous Fas2 subunit to the proteasome is Ubr1. The ubiquitin-conjugating enzymes Ubc2 and Ubc4 assist the degradation process. The AAA-ATPase Cdc48 and the Hsp70 chaperone Ssa1 are crucially involved in the elimination of Fas2.