The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70.
The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70.
复制标题
DOI：
10.1038/s41598-021-96518-x
复制
发表时间：
2021-08-24
影响因子：
4.6
通讯作者：
Young JC
中科院分区：
文献类型：
--
作者：
Gonçalves CC;Sharon I;Schmeing TM;Ramos CHI;Young JC
在应激条件下的人细胞中，错误折叠的多肽可以形成潜在的细胞毒性不溶性聚集体。为了消除聚集体，HSP70分子伴侣机械提取并再溶解多肽，用于分类以重折叠或降解。酵母和细菌的小热休克蛋白（sHSP）家族分子伴侣可以结合在错误折叠的早期阶段，在聚集过程中的底物。然后，共聚集的sHSP通过HSP 70促进下游解聚。由于尚不清楚人sHSP是否具有这种活性，我们研究了人HSPB1的解聚作用。HSPB1与未折叠蛋白底物、萤火虫荧光素酶和哺乳动物乳酸脱氢酶共聚集。与HSPB1一起形成的共聚集体比在其不存在下形成的那些更小且形状更规则。重要的是，共聚集促进了底物的有效解聚和重折叠，由HSP 70领导。HSPB1本身也在解聚过程中被提取，并且不需要其同源寡聚化能力。因此，我们建议，人类sHSP是蛋白质解聚的分子伴侣网络的一个组成部分。
In human cells under stress conditions, misfolded polypeptides can form potentially cytotoxic insoluble aggregates. To eliminate aggregates, the HSP70 chaperone machinery extracts and resolubilizes polypeptides for triage to refolding or degradation. Yeast and bacterial chaperones of the small heat-shock protein (sHSP) family can bind substrates at early stages of misfolding, during the aggregation process. The co-aggregated sHSPs then facilitate downstream disaggregation by HSP70. Because it is unknown whether a human sHSP has this activity, we investigated the disaggregation role of human HSPB1. HSPB1 co-aggregated with unfolded protein substrates, firefly luciferase and mammalian lactate dehydrogenase. The co-aggregates formed with HSPB1 were smaller and more regularly shaped than those formed in its absence. Importantly, co-aggregation promoted the efficient disaggregation and refolding of the substrates, led by HSP70. HSPB1 itself was also extracted during disaggregation, and its homo-oligomerization ability was not required. Therefore, we propose that a human sHSP is an integral part of the chaperone network for protein disaggregation.
登录
查看更多内容
影响因子：
64.8
作者：
Faust, Ofrah;Abayev-Avraham, Meital;Rosenzweig, Rina
通讯作者：
Rosenzweig, Rina
影响因子：
4.1
作者：
Bryantsev, Anton L.;Kurchashova, Svetlana Yu.;Kampinga, Harm H.
通讯作者：
Kampinga, Harm H.
影响因子：
3.9
作者：
Echaniz-Laguna, Andoni;Geuens, Thomas;Stojkovic, Tanya
通讯作者：
Stojkovic, Tanya
影响因子：
82.9
作者：
d'Ydewalle, Constantin;Krishnan, Jyothsna;Van Den Bosch, Ludo
通讯作者：
Van Den Bosch, Ludo
影响因子：
4.8
作者：
Baaklini, Imad;Wong, Michael J. H.;Young, Jason C.
通讯作者：
Young, Jason C.