加拿大麥吉爾大學和日本京都大學的科學家在人體細胞內(nèi)部發(fā)現(xiàn)了一種從事質(zhì)量控制工作的酶ERdj5,，不過該酶有時工作起來太過認真,，反而成為某些遺傳性疾病的主要病因,。研究人員認為,，該發(fā)現(xiàn)有助于為一些遺傳性疾病,，比如囊腫性纖維化（遺傳性胰腺疾?。┱业叫碌闹委煼椒āＯ嚓P研究報告發(fā)表在7月25日出版的《科學》雜志上,。
兩國研究人員在細胞的內(nèi)質(zhì)網(wǎng)里發(fā)現(xiàn)了這種稱作ERdj5的酶,。內(nèi)質(zhì)網(wǎng)的作用就像細胞里的包裝廠，將蛋白質(zhì)“打包”準備好,，以便這些蛋白質(zhì)能夠有序地分布于細胞內(nèi)或細胞外,。但是，如果蛋白質(zhì)在內(nèi)質(zhì)網(wǎng)內(nèi)出現(xiàn)“打包”錯誤,，這些有缺陷的蛋白質(zhì)就必須在一個降解過程中被銷毀掉,。ERdj5酶正是在這個降解過程中發(fā)揮作用。
ERdj5酶是迄今所發(fā)現(xiàn)的第一種具有打破二硫鍵能力的蛋白質(zhì),，而正是二硫鍵將內(nèi)質(zhì)網(wǎng)中有缺陷的蛋白質(zhì)聚在一起,。參與研究工作的麥吉爾大學分子遺傳學權威專家湯瑪斯博士介紹說，ERdj5酶的功能就像一個“質(zhì)檢員”,，能夠識別出那些存在缺陷的蛋白質(zhì),，并在這些蛋白質(zhì)“上崗”前將其降解掉。
不幸的是,，這種酶有時工作起來太過認真,，對蛋白質(zhì)的質(zhì)量要求過于嚴格。比如,，一些人身上攜帶有變異型蛋白質(zhì)CFTR,，這些變異的蛋白質(zhì)雖然有損壞，但在“上崗”后仍然可以勝任工作,。但是,，過于嚴格的“質(zhì)檢員”仍然堅持將其降解掉。由于降解的是蛋白質(zhì),，而不是變異本身，因此導致了囊腫性纖維化（遺傳性胰腺疾病）,?；诖耍芯咳藛T認為,，該發(fā)現(xiàn)為治療該類遺傳性疾病找到了一條新的研究途徑,。（生物谷Bioon.com）
生物谷推薦原始出處：
Science 25 July 2008 321: 569-572 [DOI: 10.1126/science.1159293] (in Reports)
ERdj5 Is Required as a Disulfide Reductase for Degradation of Misfolded Proteins in the ER
Ryo Ushioda,1* Jun Hoseki,1,2* Kazutaka Araki,1* Gregor Jansen,3 David Y. Thomas,3 Kazuhiro Nagata1,2
Membrane and secretory proteins cotranslationally enter and are folded in the endoplasmic reticulum (ER). Misfolded or unassembled proteins are discarded by a process known as ER-associated degradation (ERAD), which involves their retrotranslocation into the cytosol. ERAD substrates frequently contain disulfide bonds that must be cleaved before their retrotranslocation. Here, we found that an ER-resident protein ERdj5 had a reductase activity, cleaved the disulfide bonds of misfolded proteins, and accelerated ERAD through its physical and functional associations with EDEM (ER degradation–enhancing -mannosidase–like protein) and an ER-resident chaperone BiP. Thus, ERdj5 is a member of a supramolecular ERAD complex that recognizes and unfolds misfolded proteins for their efficient retrotranslocation.
1 Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Japan.
2 Core Research for Evolutional Science and Technology, Japan Science Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
3 Biochemistry Department, Faculty of Medicine, McGill University, Montréal, Québec H3G 1Y6, Canada.
