日本科学家在新一期美国《科学》杂志网络版上介绍说，他们进一步探明了细胞处理缺陷蛋白质的质量控制机制。这一成果可能有助于寻找治疗阿尔茨海默氏症等疾病的新方法。
日本京都大学教授永田和宏等人发现，细胞内质网上有3种蛋白质巧妙分工合作，检测、分解并处理有缺陷的蛋白质，承担着对细胞内的蛋白质进行质量管理的任务。内质网是分布在细胞质中的膜性管道系统，具有参与蛋白质合成、加工、包装等功能。
永田和宏等科学家此前曾发现，一种名为“EDEM”的蛋白质能检测出细胞内有缺陷的蛋白质，相当于细胞内蛋白质的“质量总监”。他们在新研究中又发现，“ERdj5”等另外两种酶，在处理缺陷蛋白质的过程中也发挥着重要作用。
科学家说，这两种酶能拆开缺陷蛋白质，使之成为一根细长的分子链，并把分子链运出内质网，进行废弃处理。其中，“ERdj5”是迄今发现的第一种能够拆开缺陷蛋白质中二硫键的酶。拆开二硫键使得缺陷蛋白质能够被完全分解，而且分解出的氨基酸还能再次用于合成其他蛋白质。
基因异常等原因会导致机体错误地合成有缺陷的蛋白质，这些蛋白质如果在神经等处堆积，会引起阿尔茨海默氏症和帕金森氏症等疾病。永田和宏认为，将来如果能够依靠药物激活细胞内的质量控制机制，就有可能找到针对这些疾病的新疗法。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
