GroE modulates kinetic partitioning of folding intermediates between alternative states to maximize the yield of biologically active protein
GroE modulates kinetic partitioning of folding intermediates between alternative states to maximize the yield of biologically active protein
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DOI：
10.1006/jmbi.1997.1007
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发表时间：
1997-05-16
影响因子：
5.6
通讯作者：
Baldwin, TO
中科院分区：
文献类型：
--
作者：
Fedorov, AN;Baldwin, TO
分子伴侣功能的中心问题是折叠多肽沿着生产性途径的分配可以最大化而非生产性折叠途径最小化的机制。我们已经发现GroE分子伴侣能够加速细菌荧光素酶α p异二聚体形成的生产途径的速率。在中间温度下，在生产途径和非生产途径导致二聚化能力的单体形式的亚基共存，GroE提高天然酶的产量，同时最大限度地减少错误折叠的蛋白质的产量。这些结果表明，GroE释放的亚基的形式能够实现天然结构的速度比最初的伴侣结合的形式。在较高的温度下，天然酶是稳定的，但二聚反应减弱，GroE不能迫使生产性折叠反应发生。然而，分子伴侣降低了异二聚化不胜任物种的形成速率，从而当温度降低到允许范围时提高了活性酶的最终产率。我们的研究结果表明，分子伴侣的功能，以最大限度地提高产量的生物活性形式的蛋白质，同时保持甚至加速折叠反应的基本快速动力学的机制。(C)出版社：Academic Press Limited。
The central issue of chaperone function is the mechanism whereby partitioning of folding polypeptides along the productive pathway may be maximized, while non-productive folding pathways are minimized. We have found that the GroE chaperone is capable of accelerating the rate of the productive pathway of bacterial luciferase ap heterodimer formation. At intermediate temperatures at which the productive pathway and nonproductive pathways leading to dimerization-incompetent monomeric forms of the subunits coexist, GroE enhances the yield of native enzyme while minimizing the yield of misfolded protein. These results suggest that GroE releases the subunits in forms capable of achieving the native structure faster than the forms initially bound by the chaperone. At higher temperatures, at which the native enzyme is stable but the dimerization reaction is diminished, GroE is unable to force the productive folding reaction to occur. However, the chaperone decreases the rate of formation of the heterodimerization-incompetent species, thereby enhancing the final yield of active enzyme when the temperature is reduced to the permissive range. Our results suggest a mechanism by which the chaperone functions to maximize the yield of the biologically active form of the protein while maintaining or even accelerating the essential rapid kinetics of folding reactions. (C) 1997 Academic Press Limited.