Kaimal Jayasankar Mohanakrishnan, Kandasamy Ganapathi, Gasser Fabian, Andréasson Claes
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
Mol Cell Biol. 2017 May 16;37(11). doi: 10.1128/MCB.00027-17. Print 2017 Jun 1.
Protein aggregation is intimately associated with cellular stress and is accelerated during aging, disease, and cellular dysfunction. Yeast cells rely on the ATP-consuming chaperone Hsp104 to disaggregate proteins together with Hsp70. Hsp110s are ancient and abundant chaperones that form complexes with Hsp70. Here we provide data showing that the Hsp110s Sse1 and Sse2 are essential for Hsp104-dependent protein disaggregation. Following heat shock, complexes of Hsp110 and Hsp70 are recruited to protein aggregates and function together with Hsp104 in the disaggregation process. In the absence of Hsp110, targeting of Hsp70 and Hsp104 to the aggregates is impaired, and the residual Hsp104 that still reaches the aggregates fails to disaggregate. Thus, coordinated activities of both Hsp104 and Hsp110 are required to reactivate aggregated proteins. These findings have important implications for the understanding of how eukaryotic cells manage misfolded and amyloid proteins.
蛋白质聚集与细胞应激密切相关，并且在衰老、疾病和细胞功能障碍过程中会加速。酵母细胞依靠消耗ATP的伴侣蛋白Hsp104与Hsp70一起使蛋白质解聚。Hsp110是古老且丰富的伴侣蛋白，可与Hsp70形成复合物。在此，我们提供的数据表明，Hsp110的Sse1和Sse2对于Hsp104依赖的蛋白质解聚至关重要。热休克后，Hsp110和Hsp70的复合物被募集到蛋白质聚集体上，并在解聚过程中与Hsp104协同发挥作用。在没有Hsp110的情况下，Hsp70和Hsp104向聚集体的靶向作用受损，并且仍然到达聚集体的残余Hsp104无法解聚。因此，Hsp104和Hsp110的协同活动是重新激活聚集蛋白所必需的。这些发现对于理解真核细胞如何处理错误折叠的蛋白质和淀粉样蛋白具有重要意义。
