Dicarboxylic amino acids and glycine-betaine regulate chaperone-mediated protein-disaggregation under stress
Dicarboxylic amino acids and glycine-betaine regulate chaperone-mediated protein-disaggregation under stress
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DOI：
10.1046/j.1365-2958.2003.03553.x
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发表时间：
2003-07-01
影响因子：
3.6
通讯作者：
Goloubinoff, P
中科院分区：
文献类型：
--
作者：
Diamant, S;Rosenthal, D;Goloubinoff, P
由ClpB和DnaK + DnaJ + GrpE组成的分子伴侣网络的活性蛋白解聚对于体外和大肠杆菌细胞中应激诱导的蛋白聚集体的恢复是必不可少的。谷氨酸钾和甘氨酸甜菜碱（甜菜碱）在盐胁迫细胞中自然积累。除了对天然蛋白质提供热保护之外，我们发现这些渗透剂可以强烈且特异性地激活ClpB，导致伴侣介导的蛋白质解聚的效率增加。此外，通过损害ClpB低聚物的稳定性来抑制分子伴侣网络的因素，例如天然多胺、稀释或高盐，被谷氨酸钾或甜菜碱有效地抵消。组合的保护，反负和净活化作用的K-谷氨酸盐和甜菜碱，允许蛋白质解聚和重折叠的热休克温度下，否则会导致蛋白质聚集在体外和细胞。因此，嗜热微生物可能受益于耐热性渗压剂激活的分子伴侣机制，该机制可以积极拯救蛋白质聚集体，正确地重折叠并在热休克条件下将其保持在天然状态。
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.