Structure and Dynamics of the ATP-Bound Open Conformation of Hsp70 Chaperones
Structure and Dynamics of the ATP-Bound Open Conformation of Hsp70 Chaperones
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DOI：
10.1016/j.molcel.2012.09.023
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发表时间：
2012-12-28
期刊：
影响因子：
16
通讯作者：
Mayer, Matthias P.
中科院分区：
文献类型：
--
作者：
Kityk, Roman;Kopp, Juergen;Mayer, Matthias P.
Hsp70分子伴侣功能的核心是其多肽底物结合域(SBD)的开放构象和闭合构象之间的转换，这是通过变构机制通过其核苷酸结合域(NBD)上的ATP结合和水解来调节的。尽管Hsp70的闭合构象结构已经得到了很好的研究，但开放构象仍然难以捉摸。在这里，我们报道了大肠杆菌Hsp70同源物DNAK与ATP结合的开放构象的2.4埃晶体结构。在开放的DNAK结构中，SBD的β-折叠和α-螺旋LID亚域相互分离，并对接到NBD的不同面上。β片亚结构域与NBD之间的接触揭示了变构调节的机制。此外，我们还证明了β-折叠和α-螺旋LID亚域与NBD的对接是一个受肽和蛋白质底物影响的顺序过程。
Central to the chaperone function of Hsp70s is the transition between open and closed conformations of their polypeptide substrate binding domain (SBD), which is regulated through an allosteric mechanism via ATP binding and hydrolysis in their nucleotide binding domain (NBD). Although the structure of the closed conformation of Hsp70s is well studied, the open conformation has remained elusive. Here, we report on the 2.4 angstrom crystal structure of the ATP-bound open conformation of the Escherichia coli Hsp70 homolog DnaK. In the open DnaK structure, the beta sheet and alpha-helical lid subdomains of the SBD are detached from one another and docked to different faces of the NBD. The contacts between the beta sheet subdomain and the NBD reveal the mechanism of allosteric regulation. In addition, we demonstrate that docking of the beta sheet and a-helical lid subdomains to the NBD is a sequential process influenced by peptide and protein substrates.