Lee Sukyeong, Sowa Mathew E, Choi Jae-Mun, Tsai Francis T F
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston TX, 77030, USA.
J Struct Biol. 2004 Apr-May;146(1-2):99-105. doi: 10.1016/j.jsb.2003.11.016.
ClpB and Hsp104 (ClpB/Hsp104) are essential proteins of the heat-shock response and belong to the class 1 family of Clp/Hsp100 AAA+ ATPases. Members of this family form large ring structures and contain two AAA+ modules, which consist of a RecA-like nucleotide-binding domain (NBD) and an alpha-helical domain. Furthermore, ClpB/Hsp104 has a longer middle region, the ClpB/Hsp104-linker, which is essential for chaperone activity. Unlike other Clp/Hsp100 proteins, however, ClpB/Hsp104 neither associates with a cellular protease nor directs the degradation of its substrate proteins. Rather, ClpB/Hsp104 is a bona fide molecular chaperone, which has the remarkable ability to rescue proteins from an aggregated state. The full recovery of these proteins requires the assistance of the cognate DnaK/Hsp70 chaperone system. The mechanism of this "bi-chaperone" network, however, remains elusive. Here we review the current understanding of the structure-function relationship of the ClpB/Hsp104 molecular chaperone and its role in protein disaggregation.
ClpB和Hsp104（ClpB/Hsp104）是热休克反应的必需蛋白，属于Clp/Hsp100 AAA+ ATP酶的1类家族。该家族成员形成大环结构，包含两个AAA+模块，由一个类RecA核苷酸结合结构域（NBD）和一个α-螺旋结构域组成。此外，ClpB/Hsp104有一个更长的中间区域，即ClpB/Hsp104连接区，这对伴侣活性至关重要。然而，与其他Clp/Hsp100蛋白不同，ClpB/Hsp104既不与细胞蛋白酶结合，也不指导其底物蛋白的降解。相反，ClpB/Hsp104是一种真正的分子伴侣，具有从聚集状态拯救蛋白的非凡能力。这些蛋白的完全恢复需要同源DnaK/Hsp70伴侣系统的协助。然而，这种“双伴侣”网络的机制仍然难以捉摸。在这里，我们综述了目前对ClpB/Hsp104分子伴侣的结构-功能关系及其在蛋白解聚中的作用的理解。
