Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Mol Cell. 2010 Sep 10;39(5):821-7. doi: 10.1016/j.molcel.2010.07.019. Epub 2010 Aug 12.
Ubiquitin (Ub) provides the recognition and specificity required to deliver proteins to the eukaryotic proteasome for destruction. Prokaryotic ubiquitin-like protein (Pup) is functionally analogous to Ub in Mycobacterium tuberculosis (Mtb), as it dooms proteins to the Mtb proteasome. Studies suggest that Pup and Ub do not share similar mechanisms of activation and conjugation to target proteins. Dop (deamidase of Pup; Mtb Rv2112c/MT2172) deamidates the C-terminal glutamine of Pup to glutamate, preparing it for ligation to target proteins by proteasome accessory factor A (PafA). While studies have shed light on the conjugation of Pup to proteins, it was not known if Pup could be removed from substrates in a manner analogous to the deconjugation of Ub from eukaryotic proteins. Here, we show that Mycobacteria have a "depupylase" activity provided by Dop. The discovery of a depupylase strengthens the parallels between the Pup- and Ub-tagging systems of prokaryotes and eukaryotes, respectively.
泛素 (Ub) 提供了识别和特异性，将蛋白质递送到真核蛋白酶体进行降解。原核泛素样蛋白 (Pup) 在功能上类似于结核分枝杆菌 (Mtb) 中的 Ub，因为它使蛋白质注定要被 Mtb 蛋白酶体破坏。研究表明，Pup 和 Ub 没有类似的激活和连接到靶蛋白的机制。Dop（Pup 的脱酰胺酶；Mtb Rv2112c/MT2172）使 Pup 的 C 末端谷氨酰胺脱酰胺为谷氨酸，为其与蛋白酶体辅助因子 A（PafA）连接到靶蛋白做好准备。虽然研究已经阐明了 Pup 与蛋白质的连接，但尚不清楚 Pup 是否可以以类似于从真核蛋白质中去除 Ub 的方式从底物中去除。在这里，我们表明分枝杆菌具有 Dop 提供的“脱泛素酶”活性。脱泛素酶的发现增强了原核生物和真核生物中 Pup 和 Ub 标记系统之间的相似性。
