Vogel Markus, Bukau Bernd, Mayer Matthias P
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBI), Heidelberg, Germany.
Mol Cell. 2006 Feb 3;21(3):359-67. doi: 10.1016/j.molcel.2005.12.017.
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.
热休克蛋白70（Hsp70）伴侣功能的关键在于两种构象状态之间由核苷酸调节的转变，即ATP结合状态，其底物的结合和解离速率较高；以及ADP结合状态，其结合和解离速率比前者低两到三个数量级。两种状态之间的自发转变极其缓慢，这表明调节该转变的开关存在高能量屏障。在这里，我们提供证据表明，ATP酶结构域中一个普遍保守的脯氨酸构成了该开关，它会根据ATP的结合和水解呈现交替构象。脯氨酸的构象通过一个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关闭构象，从而调节Hsp70的伴侣活性。
