Allosteric regulation of Hsp70 chaperones by a proline switch
Allosteric regulation of Hsp70 chaperones by a proline switch
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DOI：
10.1016/j.molcel.2005.12.017
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发表时间：
2006-02-03
期刊：
影响因子：
16
通讯作者：
Mayer, MP
中科院分区：
文献类型：
--
作者：
Vogel, M;Bukau, B;Mayer, MP
Hsp70分子伴侣的功能的关键是两种构象状态之间的核苷酸调节的转换，ATP结合状态与高的缔合和解离速率的底物和ADP结合状态与两个和三个数量级较低的缔合和解离速率。两种状态之间的自发跃迁非常慢，表明调节跃迁的开关具有很高的能垒。在这里，我们提供的证据表明，普遍保守的脯氨酸在ATP酶结构域构成的开关，假设交替构象响应ATP结合和水解。脯氨酸的构象通过不变的精氨酸作为中继起作用，决定并稳定底物结合结构域的开放和闭合构象，从而调节Hsp70的伴侣活性。
Crucial to the function of Hsp70 chaperones is the nucleotide-regulated transition between two conformational states, the ATP bound state with high association and dissociation rates for substrates and the ADP bound state with two and three orders of magnitude lower association and dissociation rates. The spontaneous transition between the two states is extremely slow, indicating a high energy barrier for the switch that regulates the transition. Here we provide evidence that a universally conserved proline in the ATPase domain constitutes the switch that assumes alternate conformations in response to ATP binding and hydrolysis. The conformation of the proline, acting through an invariant arginine as relay, determines and stabilizes the opened and closed conformation of the substrate binding domain and thereby regulates the chaperone activity of Hsp70.