Structural basis for the cooperation of Hsp70 and Hsp110 chaperones in protein folding
Structural basis for the cooperation of Hsp70 and Hsp110 chaperones in protein folding
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DOI：
10.1016/j.cell.2008.05.022
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发表时间：
2008-06-13
期刊：
影响因子：
64.5
通讯作者：
Bracher, Andreas
中科院分区：
文献类型：
--
作者：
Polier, Sigrun;Dragovic, Zdravko;Bracher, Andreas
Hsp70的蛋白质折叠受到辅伴侣蛋白的严格控制，辅伴侣蛋白包括触发ATP水解的J结构域蛋白和从Hsp70去除ADP的核苷酸交换因子（NEF）。在这里，我们提出的晶体结构的酵母NEF Sse1p（热休克蛋白110）在复杂的核苷酸结合结构域（NBD）的热休克蛋白70。Hsp110蛋白与Hsp70同源，由NBD、β夹心结构域和三螺旋束结构域（3HBD）组成。在复合物中，Sse1p的NBD与ATP结合，并且与3HBD一起，它包含Hsp70的NBD，诱导打开和从Hsp70释放结合的ADP。消除NEF活性的突变是致命的，因此将Hsp70上的核苷酸交换定义为Sse1p的基本功能。我们的数据表明，Sse1p不采用典型的热休克蛋白70的核苷酸依赖性变构和肽结合模式，并与Sse1p的底物的直接相互作用可能支持热休克蛋白70辅助蛋白折叠在一个合作的过程。
Protein folding by Hsp70 is tightly controlled by cochaperones, including J-domain proteins that trigger ATP hydrolysis and nucleotide exchange factors (NEFs) that remove ADP from Hsp70. Here we present the crystal structure of the yeast NEF Sse1p (Hsp110) in complex with the nucleotide-binding domain (NBD) of Hsp70. Hsp110 proteins are homologous to Hsp70s and consist of an NBD, a beta sandwich domain, and a three helix bundle domain (3HBD). In the complex, the NBD of Sse1p is ATP bound, and together with the 3HBD it embraces the NBD of Hsp70, inducing opening and the release of bound ADP from Hsp70. Mutations that abolish NEF activity are lethal, thus defining nucleotide exchange on Hsp70 as an essential function of Sse1p. Our data suggest that Sse1p does not employ the nucleotide-dependent allostery and peptide-binding mode of canonical Hsp70s, and that direct interactions of substrate with Sse1p may support Hsp70-assisted protein folding in a cooperative process.