Multi-layered molecular mechanisms of polypeptide holding, unfolding and disaggregation by HSP70/HSP110 chaperones.
Multi-layered molecular mechanisms of polypeptide holding, unfolding and disaggregation by HSP70/HSP110 chaperones.
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DOI：
10.3389/fmolb.2015.00029
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发表时间：
2015
影响因子：
5
通讯作者：
Goloubinoff P
中科院分区：
文献类型：
--
作者：
Finka A;Sharma SK;Goloubinoff P
HSP70/HSP110家族的成员（HSP70）形成了伴侣网络的中心枢纽，控制着细菌和真核细胞中含有atp的区室的蛋白质静止的各个方面。热诱导型HSP70 （HSPA1A）及其主要同源物细胞质HSC70 （HSPA8）、内质网BIP （HSPA5）、线粒体mHSP70 （HSPA9）和相关的hsp110 （HSPHs）贡献了约3%的人细胞总蛋白质量。hsp70执行大量的细胞管理功能，例如协助适当的新生折叠，蛋白质复合物的组装和拆卸，将多肽从核糖体中拉出并穿过膜孔，激活和灭活信号蛋白并控制其降解。hsp70可以诱导网格蛋白笼、激素受体和转录因子等折叠蛋白构象的结构改变，从而调节发育和癌症过程中的囊泡运输、激素信号传导和细胞分化。为了携带如此多样的细胞内保和压力相关功能，hsp70充当atp燃料的展开纳米机器，能够在不同的折叠状态之间切换多肽。在应激过程中，hsp70可以结合（保持）并阻止错误折叠蛋白的聚集，然后单独或与其他展开的伴侣蛋白协同作用来溶解蛋白质聚集物。在这里，我们讨论了常见的atp依赖机制，通过夹紧展开和熵拉展开，通过这些机制，hsp70可以明显地将各种可选折叠和错误折叠的多肽转化为不同的活性构象。了解hsp70如何阻止细胞毒性蛋白聚集体的形成、拉伸、展开并将其溶解为无害的物种，是设计针对蛋白质构象疾病的治疗方法的核心。
Members of the HSP70/HSP110 family (HSP70s) form a central hub of the chaperone network controlling all aspects of proteostasis in bacteria and the ATP-containing compartments of eukaryotic cells. The heat-inducible form HSP70 (HSPA1A) and its major cognates, cytosolic HSC70 (HSPA8), endoplasmic reticulum BIP (HSPA5), mitochondrial mHSP70 (HSPA9) and related HSP110s (HSPHs), contribute about 3% of the total protein mass of human cells. The HSP70s carry out a plethora of housekeeping cellular functions, such as assisting proper de novo folding, assembly and disassembly of protein complexes, pulling polypeptides out of the ribosome and across membrane pores, activating and inactivating signaling proteins and controlling their degradation. The HSP70s can induce structural changes in alternatively folded protein conformers, such as clathrin cages, hormone receptors and transcription factors, thereby regulating vesicular trafficking, hormone signaling and cell differentiation in development and cancer. To carry so diverse cellular housekeeping and stress-related functions, the HSP70s act as ATP-fuelled unfolding nanomachines capable of switching polypeptides between different folded states. During stress, the HSP70s can bind (hold) and prevent the aggregation of misfolding proteins and thereafter act alone or in collaboration with other unfolding chaperones to solubilize protein aggregates. Here, we discuss the common ATP-dependent mechanisms of holding, unfolding-by-clamping and unfolding-by-entropic pulling, by which the HSP70s can apparently convert various alternatively folded and misfolded polypeptides into differently active conformers. Understanding how HSP70s can prevent the formation of cytotoxic protein aggregates, pull, unfold, and solubilize them into harmless species is central to the design of therapies against protein conformational diseases.
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影响因子：
4.8
作者：
Dittmar, KD;Banach, M;Pratt, WB
通讯作者：
Pratt, WB
影响因子：
6.8
作者：
Bellotti, Vittorio;Chiti, Fabrizio
通讯作者：
Chiti, Fabrizio
DOI：
10.1074/mcp.m111.014050
发表时间：
2012-03
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Geiger T;Wehner A;Schaab C;Cox J;Mann M
通讯作者：
Mann M
影响因子：
3.3
作者：
Arike, L.;Valgepea, K.;Vilu, R.
通讯作者：
Vilu, R.
影响因子：
5.6
作者：
Elsner, Shira;Simian, Dana;Azem, Abdussalam
通讯作者：
Azem, Abdussalam