The molecular chaperone Hsp 104 -: A molecular machine for protein disaggregation
The molecular chaperone Hsp 104 -: A molecular machine for protein disaggregation
复制标题
DOI：
10.1016/j.jsb.2006.02.004
复制
发表时间：
2006-10-01
影响因子：
3
通讯作者：
Walter, Stefan
中科院分区：
文献类型：
--
作者：
Boesl, Benjamin;Grimminger, Valerie;Walter, Stefan
在1996年5月关于“分子伴侣和热休克反应”的冷泉港会议上，Susan Lindquist提出了她的小组已经研究了几年的酵母分子伴侣HSP 104能够溶解蛋白质聚集体的证据（格洛弗，JR.，Lindquist，S.，1998. Hsp 104，Hsp 70和Hsp 40：一种新的分子伴侣系统，拯救以前聚集的蛋白质。Cell 94，73-82）。在许多参与者中，这一消息刺激了从决定怀疑到完全不相信的反应，因为蛋白质聚集被广泛认为是一个不可逆的过程。几年后，出版物，不可否认，苏珊是正确的。Hsp 104是一种ATP依赖的分子机器，与Hsp 70和Hsp 40合作，从蛋白质聚集体中提取多肽链并促进其重折叠，尽管这一过程的分子细节仍然知之甚少。同时，已经在细菌（ClpB）、线粒体（Hsp 78）和植物的胞质溶胶（Hsp 101）中鉴定了Hsp 104的密切同源物，但有趣的是在动物细胞的胞质溶胶中没有（Mosser，D.D.，何，S.，格洛弗，J.R.，2004.酿酒酵母Hsp 104增强人类细胞的伴侣能力并抑制热应激诱导的促凋亡信号传导。Biochemistry 43，8107-8115）。Hsp 104在维持酵母朊病毒中起重要作用的观察结果（参见James Shorter在本期中的评论）已经吸引了对这种ATP依赖性伴侣的分子机制的更多关注（Besoff，Y.O.，Lindquist，S.L.，小野，B.，Inge-Vechtomov，S.G.，Liebman，S.W.，1995.伴侣蛋白Hsp 104在酵母朊病毒样因子[PSI+]繁殖中的作用。Science 268，880-884）。(c)2006年爱思唯尔公司All rights reserved.
At the Cold Spring Harbor Meeting on 'Molecular Chaperones and the Heat Shock Response' in May 1996, Susan Lindquist presented evidence that a chaperone of yeast termed Hsp104, which her group had been investigating for several years, is able to dissolve protein aggregates (Glover, JR., Lindquist, S., 1998. Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94, 73-82). Among many of the participants this news stimulated reactions reaching from decided skepticism to utter disbelief because protein aggregation was widely considered to be an irreversible process. Several years and publications later, it is undeniable that Susan had been right. Hsp104 is an ATP dependent molecular machine that-in cooperation with Hsp70 and Hsp40-extracts polypeptide chains from protein aggregates and facilitates their refolding, although the molecular details of this process are still poorly understood. Meanwhile, close homologues of Hsp104 have been identified in bacteria (ClpB), in mitochondria (Hsp78), and in the cytosol of plants (Hsp101), but intriguingly not in the cytosol of animal cells (Mosser, D.D., Ho, S., Glover, J.R., 2004. Saccharomyces cerevisiae Hsp104 enhances the chaperone capacity of human cells and inhibits heat stress-induced proapoptotic signaling. Biochemistry 43, 8107-8115). Observations that Hsp104 plays an essential role in the maintenance of yeast prions (see review by James Shorter in this issue) have attracted even more attention to the molecular mechanism of this ATP dependent chaperone (Chernoff, Y.O., Lindquist, S.L., Ono, B., Inge-Vechtomov, S.G., Liebman, S.W., 1995. Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [PSI+]. Science 268, 880-884). (c) 2006 Elsevier Inc. All rights reserved.