Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation.
Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation.
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DOI：
10.3389/fmolb.2015.00022
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发表时间：
2015
影响因子：
5
通讯作者：
Bukau B
中科院分区：
文献类型：
--
作者：
Mogk A;Kummer E;Bukau B
单细胞和固着生物体特别暴露于环境应激，如热休克，导致错误折叠的蛋白质种类的积累和聚集。为了抵抗蛋白质聚集，细菌、真菌和植物编码由ATP依赖性Hsp 70和六聚体Hsp 100（ClpB/Hsp 104）分子伴侣组成的双分子伴侣系统，其拯救聚集的蛋白质并为细胞提供耐热性。伴侣以分层的方式起作用，其中Hsp 70分子伴侣首先覆盖蛋白质聚集体的表面，然后通过直接的物理相互作用招募Hsp 100。Hsp 100蛋白通过其独特的M结构域与Hsp 70的ATP酶结构域结合。这个额外的结构域作为一个分子切换功能，变构控制ATP酶和Hsp 100的线程活动。相邻的M-结构域和ATP酶环之间的相互作用使Hsp 100保持在抑制状态，表现出低ATP周转。分子间M-结构域相互作用的断裂和M-结构域从ATP酶环的解离解除阻遏并允许Hsp 70相互作用。热休克蛋白70结合反过来稳定热休克蛋白100在活化状态和引物热休克蛋白100 ATP酶结构域的高活性底物相互作用。Hsp 70因此偶联Hsp 100底物结合和马达激活。热休克蛋白100的激活可能依赖于增加亚基的合作，导致高ATP周转率和线程的权力。这种Hsp 70介导的Hsp 100活性控制对于细胞活力至关重要，因为永久活化的Hsp 100变体是有毒的。Hsp 100的活化需要同时结合多个Hsp 70配偶体，将高Hsp 100活性限制在蛋白质聚集体的表面，并确保Hsp 100底物特异性。
Unicellular and sessile organisms are particularly exposed to environmental stress such as heat shock causing accumulation and aggregation of misfolded protein species. To counteract protein aggregation, bacteria, fungi, and plants encode a bi-chaperone system composed of ATP-dependent Hsp70 and hexameric Hsp100 (ClpB/Hsp104) chaperones, which rescue aggregated proteins and provide thermotolerance to cells. The partners act in a hierarchic manner with Hsp70 chaperones coating first the surface of protein aggregates and next recruiting Hsp100 through direct physical interaction. Hsp100 proteins bind to the ATPase domain of Hsp70 via their unique M-domain. This extra domain functions as a molecular toggle allosterically controlling ATPase and threading activities of Hsp100. Interactions between neighboring M-domains and the ATPase ring keep Hsp100 in a repressed state exhibiting low ATP turnover. Breakage of intermolecular M-domain interactions and dissociation of M-domains from the ATPase ring relieves repression and allows for Hsp70 interaction. Hsp70 binding in turn stabilizes Hsp100 in the activated state and primes Hsp100 ATPase domains for high activity upon substrate interaction. Hsp70 thereby couples Hsp100 substrate binding and motor activation. Hsp100 activation presumably relies on increased subunit cooperation leading to high ATP turnover and threading power. This Hsp70-mediated activity control of Hsp100 is crucial for cell viability as permanently activated Hsp100 variants are toxic. Hsp100 activation requires simultaneous binding of multiple Hsp70 partners, restricting high Hsp100 activity to the surface of protein aggregates and ensuring Hsp100 substrate specificity.
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DOI：
10.1016/j.bbamcr.2011.06.007
发表时间：
2012-01
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Baker TA;Sauer RT
通讯作者：
Sauer RT
影响因子：
64.5
作者：
DeSantis ME;Leung EH;Sweeny EA;Jackrel ME;Cushman-Nick M;Neuhaus-Follini A;Vashist S;Sochor MA;Knight MN;Shorter J
通讯作者：
Shorter J
影响因子：
11.4
作者：
Hattendorf, DA;Lindquist, SL
通讯作者：
Lindquist, SL
影响因子：
3
作者：
Biter, Amadeo B.;Lee, Jungsoon;Lee, Sukyeong
通讯作者：
Lee, Sukyeong
影响因子：
4.8
作者：
Franzmann, Titus M.;Czekalla, Anna;Walter, Stefan G.
通讯作者：
Walter, Stefan G.