A molecular device for the redox quality control of GroEL/ES substrates.
A molecular device for the redox quality control of GroEL/ES substrates.
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用于 GroEL/ES 底物氧化还原质量控制的分子装置。
作者：
Dupuy,Emile;VanderVerren,SanderEgbert;Lin,Jiusheng;Wilson,MarkAlan;Dachsbeck,AlixVincent;Viela,Felipe;Latour,Emmanuelle;Gennaris,Alexandra;Vertommen,Didier;Dufrêne,YvesFrédéric;Iorga,BogdanIuliu;Goemans,CamilleVéronique;Rem
Hsp60分子伴侣蛋白及其辅助因子Hsp10在所有活细胞中协助蛋白质折叠，构成了分子伴侣蛋白的范例。尽管对它们的结构和机制进行了广泛的研究，但关于这些伴侣蛋白如何促进折叠的关键问题仍然没有解决。在这里，我们报告了细菌Hsp60伴侣蛋白GroEL与伴侣蛋白CnoX形成了一个稳定的、功能相关的复合体，CnoX是一种结合了伴侣和氧化还原功能的蛋白质。Groes(Hsp10辅因子)与GroEL结合可诱导CnoX的释放。冷冻电子显微镜提供了关于GroEL-cnox复合体的关键结构信息，表明cnox通过高度保守的C末端α-螺旋与GroEL结合在底物结合部位之外。此外，我们还发现了与GroEL结合的CnoX与GroEL底物形成混合二硫化物的络合物，这表明CnoX可能作为GroEL的氧化还原质量控制插件发挥作用。真核生物中存在着与CnoX具有相同结构特征的蛋白质，这表明Hsp60分子插件在进化过程中是保守的。
Hsp60 chaperonins and their Hsp10 cofactors assist protein folding in all living cells, constituting the paradigmatic example of molecular chaperones. Despite extensive investigations of their structure and mechanism, crucial questions regarding how these chaperonins promote folding remain unsolved. Here, we report that the bacterial Hsp60 chaperonin GroEL forms a stable, functionally relevant complex with the chaperedoxin CnoX, a protein combining a chaperone and a redox function. Binding of GroES (Hsp10 cofactor) to GroEL induces CnoX release. Cryoelectron microscopy provided crucial structural information on the GroEL-CnoX complex, showing that CnoX binds GroEL outside the substrate-binding site via a highly conserved C-terminal α-helix. Furthermore, we identified complexes in which CnoX, bound to GroEL, forms mixed disulfides with GroEL substrates, indicating that CnoX likely functions as a redox quality-control plugin for GroEL. Proteins sharing structural features with CnoX exist in eukaryotes, suggesting that Hsp60 molecular plugins have been conserved through evolution.