Hsp70 targets Hsp100 chaperones to substrates for protein disaggregation and prion fragmentation.
Hsp70 targets Hsp100 chaperones to substrates for protein disaggregation and prion fragmentation.
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Hsp70 将 Hsp100 分子伴侣靶向底物，以实现蛋白质解聚和朊病毒断裂。
DOI：
10.1083/jcb.201201074
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发表时间：
2012-08-06
期刊：
影响因子：
--
通讯作者：
Mogk A
中科院分区：
文献类型：
--
作者：
Winkler J;Tyedmers J;Bukau B;Mogk A
Hsp 70系统将ClpB/Hsp 104募集到应激诱导的蛋白质聚集体和朊病毒原纤维的表面。细菌、酵母和植物中的Hsp 100和Hsp 70分子伴侣合作以重新激活聚集的蛋白质。解聚依赖于Hsp 70功能和聚集的多肽通过Hsp 100 AAA+六聚体的孔的ATP依赖性穿线。在酵母中，这两种分子伴侣也通过纤维断裂促进朊病毒的繁殖，但它们的功能相互作用是有争议的。在这里，我们证明，Hsp 70分子伴侣是必不可少的物种特异性靶向其Hsp 100伴侣分子伴侣ClpB和Hsp 104，分别在体内热诱导的蛋白质聚集体。酵母中的Hsp 70失活也废除了Hsp 104对几乎所有测试的朊病毒的靶向，并降低了原纤维的流动性，这表明Hsp 104的原纤维片段化需要Hsp 70。Sup 35朊病毒是独特的，允许Hsp 70独立协会的Hsp 104通过其N-末端结构域，然而，这是非生产性的。Hsp 104的过量生产甚至超过了Hsp 70与Sup 35朊病毒的结合，这解释了为什么这种情况会阻止Sup 35断裂并导致朊病毒固化。我们的研究结果表明，在蛋白质聚集体和朊病毒原纤维的表面Hsp 70-Hsp 100合作的保守机制。
The Hsp70 system recruits ClpB/Hsp104 to the surface of stress-induced protein aggregates and prion fibrils. Hsp100 and Hsp70 chaperones in bacteria, yeast, and plants cooperate to reactivate aggregated proteins. Disaggregation relies on Hsp70 function and on ATP-dependent threading of aggregated polypeptides through the pore of the Hsp100 AAA+ hexamer. In yeast, both chaperones also promote propagation of prions by fibril fragmentation, but their functional interplay is controversial. Here, we demonstrate that Hsp70 chaperones were essential for species-specific targeting of their Hsp100 partner chaperones ClpB and Hsp104, respectively, to heat-induced protein aggregates in vivo. Hsp70 inactivation in yeast also abrogated Hsp104 targeting to almost all prions tested and reduced fibril mobility, which indicates that fibril fragmentation by Hsp104 requires Hsp70. The Sup35 prion was unique in allowing Hsp70-independent association of Hsp104 via its N-terminal domain, which, however, was nonproductive. Hsp104 overproduction even outcompeted Hsp70 for Sup35 prion binding, which explains why this condition prevented Sup35 fragmentation and caused prion curing. Our findings indicate a conserved mechanism of Hsp70–Hsp100 cooperation at the surface of protein aggregates and prion fibrils.
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影响因子：
4.8
作者：
Barnett, ME;Nagy, M;Zolkiewski, M
通讯作者：
Zolkiewski, M
影响因子：
16
作者：
Cashikar, AG;Schirmer, EC;Lindquist, SL
通讯作者：
Lindquist, SL
影响因子：
16.8
作者：
Doyle, Shannon M.;Shorter, James;Wickner, Sue
通讯作者：
Wickner, Sue
影响因子：
64.5
作者：
Glover, JR;Lindquist, S
通讯作者：
Lindquist, S
DOI：
10.1073/pnas.0808934105
发表时间：
2008-10-28
影响因子：
11.1
作者：
Higurashi, Takashi;Hines, Justin K.;Craig, Elizabeth A.
通讯作者：
Craig, Elizabeth A.