Minami M, Nakamura M, Emori Y, Minami Y
Department of Biochemistry, Oita Medical University, Oita, Japan.
Eur J Biochem. 2001 Apr;268(8):2520-4. doi: 10.1046/j.1432-1327.2001.02145.x.
Hsp90 is able to bind partially unfolded firefly luciferase and maintain it in a refoldable state; the subsequent successive action of the 20S proteasome activator PA28, Hsc70 and Hsp40 enables its refolding. Hsp90 possesses two chaperone sites in the N- and C-terminal domains that prevent the aggregation of denatured proteins. Here we show that both chaperone sites of Hsp90 are effective not only in capturing thermally denatured luciferase, but also in holding it in a state prerequisite for the successful refolding process mediated by PA28, Hsc70 and Hsp40. In contrast, the heat-induced activity of Hsp90 to bind chemically denature dihydrofolate reductase efficiently and prevent its rapid spontaneous refolding was detected in the N-terminal site of Hsp90 only, while the C-terminal site was without effect. Thus it is most likely that both the N- and C-terminal chaperone sites may contribute to Hsp90 function as holder chaperones, however, in a significantly distinct manner.
热休克蛋白90（Hsp90）能够结合部分未折叠的萤火虫荧光素酶，并使其保持在可重折叠状态；随后，20S蛋白酶体激活剂PA28、热休克同源蛋白70（Hsc70）和热休克蛋白40（Hsp40）的相继作用使其能够重折叠。Hsp90在N端和C端结构域拥有两个伴侣蛋白位点，可防止变性蛋白聚集。在此我们表明，Hsp90的两个伴侣蛋白位点不仅在捕获热变性的荧光素酶方面有效，而且在将其保持在由PA28、Hsc70和Hsp40介导的成功重折叠过程的先决状态方面也有效。相比之下，仅在Hsp90的N端位点检测到热诱导的Hsp90结合化学变性二氢叶酸还原酶并有效防止其快速自发重折叠的活性，而C端位点则无此作用。因此，很可能N端和C端伴侣蛋白位点都可能以显著不同的方式对Hsp90作为保持型伴侣蛋白的功能做出贡献。
