Diamant Sophia, Rosenthal David, Azem Abdussalam, Eliahu Noa, Ben-Zvi Anat Peres, Goloubinoff Pierre
Department of Plant Sciences, Institute of Life Science, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
Mol Microbiol. 2003 Jul;49(2):401-10. doi: 10.1046/j.1365-2958.2003.03553.x.
Active protein-disaggregation by a chaperone network composed of ClpB and DnaK + DnaJ + GrpE is essential for the recovery of stress-induced protein aggregates in vitro and in Escherichia coli cells. K-glutamate and glycine-betaine (betaine) naturally accumulate in salt-stressed cells. In addition to providing thermo-protection to native proteins, we found that these osmolytes can strongly and specifically activate ClpB, resulting in an increased efficiency of chaperone-mediated protein disaggregation. Moreover, factors that inhibited the chaperone network by impairing the stability of the ClpB oligomer, such as natural polyamines, dilution, or high salt, were efficiently counteracted by K-glutamate or betaine. The combined protective, counter-negative and net activatory effects of K-glutamate and betaine, allowed protein disaggregation and refolding under heat-shock temperatures that otherwise cause protein aggregation in vitro and in the cell. Mesophilic organisms may thus benefit from a thermotolerant osmolyte-activated chaperone mechanism that can actively rescue protein aggregates, correctly refold and maintain them in a native state under heat-shock conditions.
由ClpB以及DnaK + DnaJ + GrpE组成的伴侣蛋白网络进行的活性蛋白解聚作用，对于在体外和大肠杆菌细胞中恢复应激诱导的蛋白聚集体至关重要。K-谷氨酸和甘氨酸甜菜碱（甜菜碱）在盐胁迫的细胞中自然积累。除了为天然蛋白质提供热保护外，我们发现这些渗透溶质可以强烈且特异性地激活ClpB，从而提高伴侣蛋白介导的蛋白解聚效率。此外，通过损害ClpB寡聚体稳定性来抑制伴侣蛋白网络的因素，如天然多胺、稀释或高盐，均可被K-谷氨酸或甜菜碱有效抵消。K-谷氨酸和甜菜碱的综合保护、抗负性和净激活作用，使得在热休克温度下能够进行蛋白解聚和重折叠，否则这些温度会在体外和细胞中导致蛋白聚集。因此，嗜温生物可能受益于一种耐热渗透溶质激活的伴侣蛋白机制，该机制能够在热休克条件下主动拯救蛋白聚集体，使其正确重折叠并维持在天然状态。
