Max-Planck-Institute for Medical Research, Department of Biomolecular Mechanisms, Heidelberg, Germany.
Curr Opin Struct Biol. 2010 Feb;20(1):46-53. doi: 10.1016/j.sbi.2009.12.014. Epub 2010 Jan 18.
Non-destructive dissagregation of protein aggregates is a formidable task mediated by the specialized AAA+ chaperone Hsp104/ClpB in combination with the Hsp70/DnaK chaperone system. The exact mechanism of how the hexameric Hsp104/ClpB proteins perform the task of protein disaggregation or remodeling is largely unknown. The process is ATP-dependent and tight coupling between the ATPase domains within the hexameric ring-complex could be observed. While substrate translocation through the central pore of the ring-shaped hexamer appears to be a central mechanism shared with other AAA+ proteins, a middle domain unique to Hsp104/ClpB could be involved in specific features of the Hsp/ClpB mechanism and its regulation. Recent findings underline the dynamic properties of the molecular complex and might provide a basis to understand substrate interaction, regulation of disaggregation activity, and interactions with co-chaperones.
非破坏性的蛋白质聚集体解离是一项艰巨的任务，需要专门的 AAA+ 伴侣蛋白 Hsp104/ClpB 与 Hsp70/DnaK 伴侣蛋白系统共同介导。六聚体 Hsp104/ClpB 蛋白如何执行蛋白质解聚或重塑任务的具体机制在很大程度上尚不清楚。该过程依赖于 ATP，并且可以观察到六聚体环复合物内的 ATP 酶结构域之间的紧密偶联。虽然底物通过环形六聚体的中心孔的易位似乎是与其他 AAA+ 蛋白共享的核心机制，但 Hsp104/ClpB 特有的中间结构域可能涉及 Hsp/ClpB 机制及其调节的特定特征。最近的发现强调了分子复合物的动态特性，并可能为理解底物相互作用、解聚活性的调节以及与共伴侣的相互作用提供基础。
