Howard Hughes Medical Institute Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543.
Institute of Molecular Biosciences, Mahidol University, Phuttamonthon, Nakhon Pathom 73170, Thailand.
Mol Biol Cell. 2019 Oct 1;30(21):2721-2736. doi: 10.1091/mbc.E19-04-0224. Epub 2019 Sep 4.
Despite the proliferation of proteins that can form filaments or phase-separated condensates, it remains unclear how this behavior is distributed over biological networks. We have found that 60 of the 440 yeast metabolic enzymes robustly form structures, including 10 that assemble within mitochondria. Additionally, the ability to assemble is enriched at branch points on several metabolic pathways. The assembly of enzymes at the first branch point in de novo purine biosynthesis is coordinated, hierarchical, and based on their position within the pathway, while the enzymes at the second branch point are recruited to RNA stress granules. Consistent with distinct classes of structures being deployed at different control points in a pathway, we find that the first enzyme in the pathway, PRPP synthetase, forms evolutionarily conserved filaments that are sequestered in the nucleus in higher eukaryotes. These findings provide a roadmap for identifying additional conserved features of metabolic regulation by condensates/filaments.
尽管可以形成纤维或相分离凝聚物的蛋白质大量存在，但这种行为如何在生物网络中分布仍然不清楚。我们发现，440 种酵母代谢酶中有 60 种能够形成结构，其中 10 种在线粒体中组装。此外，在几条代谢途径的分支点上，组装能力更加丰富。从头合成嘌呤生物合成中第一个分支点处的酶组装是协调的、分层的，并且基于它们在途径中的位置，而第二个分支点处的酶则被招募到 RNA 应激颗粒中。与在途径中的不同控制点部署不同结构的类别一致，我们发现该途径中的第一个酶，PRPP 合成酶，形成了进化保守的纤维，这些纤维在高等真核生物中被隔离在核内。这些发现为确定凝聚物/纤维对代谢调控的其他保守特征提供了路线图。
