Burns Kristin E, Darwin K Heran
Department of Microbiology, New York University School of Medicine, 550 First Avenue, MSB 236, New York, New York, 10016, USA.
Subcell Biochem. 2010;54:149-57. doi: 10.1007/978-1-4419-6676-6_12.
This chapter describes the identification of the first prokaryotic ubiquitin-like protein modifier, Pup, which covalently attaches to proteins to target them for destruction by a bacterial proteasome in a manner akin to ubiquitin in eukaryotes. Despite using a proteasome as the end point for proteolysis, Pup and ubiquitin differ in sequence, structure and method of activation and conjugation to protein substrates. Pup is so far the only known posttranslational protein modifier in prokaryotes and its discovery opens the door to the possibility that others are present not only for proteolysis, but also to regulate protein function or localization. Here, we discuss the putative mechanism of activation and conjugation of Pup (termed "pupylation") to target proteins. In addition, because it is unclear whether or not Pup, like ubiquitin, is recycled or degraded during substrate targeting to the proteasome, we propose methods that may identify Pup deconjugation enzymes ("depupylases"). Finally, we outline future directions for Pup research and anti-tuberculosis drug discovery.
本章描述了首个原核生物类泛素蛋白修饰因子Pup的鉴定过程，它以类似于真核生物中泛素的方式与蛋白质共价结合，将其靶向细菌蛋白酶体进行降解。尽管蛋白酶体是蛋白水解的终点，但Pup与泛素在序列、结构以及激活和与蛋白质底物结合的方式上存在差异。Pup是迄今为止原核生物中唯一已知的翻译后蛋白质修饰因子，它的发现为其他修饰因子的存在打开了可能性之门，这些修饰因子不仅参与蛋白水解，还可能调节蛋白质功能或定位。在此，我们讨论Pup（称为“Pupylation”）与靶蛋白激活和结合的推测机制。此外，由于尚不清楚Pup是否像泛素一样在底物靶向蛋白酶体的过程中被循环利用或降解，我们提出了可能鉴定Pup去结合酶（“去Pupylase”）的方法。最后，我们概述了Pup研究和抗结核药物发现的未来方向。
