日本科學(xué)家在新一期美國(guó)《科學(xué)》雜志網(wǎng)絡(luò)版上介紹說(shuō),，他們進(jìn)一步探明了細(xì)胞處理缺陷蛋白質(zhì)的質(zhì)量控制機(jī)制。這一成果可能有助于尋找治療阿爾茨海默氏癥等疾病的新方法,。
日本京都大學(xué)教授永田和宏等人發(fā)現(xiàn),，細(xì)胞內(nèi)質(zhì)網(wǎng)上有3種蛋白質(zhì)巧妙分工合作，檢測(cè),、分解并處理有缺陷的蛋白質(zhì),，承擔(dān)著對(duì)細(xì)胞內(nèi)的蛋白質(zhì)進(jìn)行質(zhì)量管理的任務(wù)。內(nèi)質(zhì)網(wǎng)是分布在細(xì)胞質(zhì)中的膜性管道系統(tǒng),，具有參與蛋白質(zhì)合成,、加工、包裝等功能,。
永田和宏等科學(xué)家此前曾發(fā)現(xiàn),，一種名為“EDEM”的蛋白質(zhì)能檢測(cè)出細(xì)胞內(nèi)有缺陷的蛋白質(zhì)，相當(dāng)于細(xì)胞內(nèi)蛋白質(zhì)的“質(zhì)量總監(jiān)”,。他們?cè)谛卵芯恐杏职l(fā)現(xiàn),，“ERdj5”等另外兩種酶，在處理缺陷蛋白質(zhì)的過(guò)程中也發(fā)揮著重要作用,。
科學(xué)家說(shuō),，這兩種酶能拆開(kāi)缺陷蛋白質(zhì)，使之成為一根細(xì)長(zhǎng)的分子鏈，并把分子鏈運(yùn)出內(nèi)質(zhì)網(wǎng),，進(jìn)行廢棄處理。其中,，“ERdj5”是迄今發(fā)現(xiàn)的第一種能夠拆開(kāi)缺陷蛋白質(zhì)中二硫鍵的酶,。拆開(kāi)二硫鍵使得缺陷蛋白質(zhì)能夠被完全分解，而且分解出的氨基酸還能再次用于合成其他蛋白質(zhì),。
基因異常等原因會(huì)導(dǎo)致機(jī)體錯(cuò)誤地合成有缺陷的蛋白質(zhì),，這些蛋白質(zhì)如果在神經(jīng)等處堆積，會(huì)引起阿爾茨海默氏癥和帕金森氏癥等疾病,。永田和宏認(rèn)為,，將來(lái)如果能夠依靠藥物激活細(xì)胞內(nèi)的質(zhì)量控制機(jī)制，就有可能找到針對(duì)這些疾病的新療法,。（生物谷Bioon.com）
生物谷推薦原始出處：
Science 25 July 2008:DOI: 10.1126/science.1159293
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.
* These authors contributed equally to this work.
