2008年,，研究人員在細菌中發(fā)現(xiàn)了一種特殊的、被稱作Pup的小蛋白,，它可以附著到其他蛋白質(zhì)上決定該蛋白命運,，進而清理蛋白質(zhì)，控制或調(diào)節(jié)細胞內(nèi)其他重要的生理過程,。最近,，瑞士聯(lián)邦理工學(xué)院（ETH Zurich）分子生物學(xué)與生物物理學(xué)研究所Eilika Weber-Ban所帶領(lǐng)的研究團隊成功發(fā)現(xiàn)了肺結(jié)核病原體結(jié)核桿菌（Mycobacterium tuberculosis）中Pup蛋白的作用機制。同時研究人員在試管內(nèi)模擬Pup結(jié)合到蛋白質(zhì)上的方式時發(fā)現(xiàn)了一種Dop新酶,。相關(guān)研究發(fā)表在2009年6月期Nature Structural & Molecular Biology上,，該結(jié)果為針對肺結(jié)核患者，尤其是病原體已產(chǎn)生抗生素耐藥性的患者制定治療策略提供了新依據(jù),。
早在80年代,，研究人員在植物、動物和人類等多細胞有機體的細胞中發(fā)現(xiàn)了與Pup蛋白類似的泛素蛋白,，并被授予了2004年諾貝爾化學(xué)獎,。但是，直到2008年年底,，研究人員才發(fā)現(xiàn)這種標(biāo)記蛋白也存在于細菌中,。瑞士聯(lián)邦理工學(xué)院研究人員發(fā)現(xiàn)，雖然細菌和人類的標(biāo)記蛋白在功能上都是確保細胞蛋白質(zhì)的降解,，但它們的結(jié)構(gòu)和作用方式卻明顯不同,。
研究人員指出，由于細菌中的蛋白標(biāo)記系統(tǒng)與人體不同,，因此針對細菌Pup系統(tǒng)的藥物對人類副作用很小,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Structural & Molecular Biology 16, 647 - 651 (2009) 17 May 2009 | doi:10.1038/nsmb.1597
Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes
Frank Striebel1, Frank Imkamp1, Markus Sutter1, Martina Steiner1, Azad Mamedov1 & Eilika Weber-Ban1
In analogy to ubiquitin in eukaryotes, the bacterial protein Pup is attached to lysine residues of substrate proteins, thereby targeting them for proteasomal degradation. It has been proposed that, before its attachment, Pup is modified by deamidation of its C-terminal glutamine to glutamate. Here we have identified Dop (locus tag Rv2112) as the specific deamidase of Pup in Mycobacterium tuberculosis. Deamidation requires ATP as a cofactor but not its hydrolysis. Furthermore, we provide experimental evidence that PafA (locus tag Rv2097) ligates deamidated Pup to the proteasomal substrate proteins FabD and PanB. This formation of an isopeptide bond requires hydrolysis of ATP to ADP, suggesting that deamidated Pup is activated for conjugation via phosphorylation of its C-terminal glutamate. By combining these enzymes, we have reconstituted the complete bacterial ubiquitin-like modification pathway in vitro, consisting of deamidation and ligation steps catalyzed by Pup deamidase (Dop) and Pup ligase (PafA).
ETH Zurich, Institute of Molecular Biology & Biophysics, Zurich, Switzerland.
