Chaperonins can catalyse the reversal of early aggregation steps when a protein misfolds.
Chaperonins can catalyse the reversal of early aggregation steps when a protein misfolds.
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当蛋白质错误折叠时，伴侣蛋白可以催化早期聚集步骤的逆转。
DOI：
10.1006/jmbi.1995.0399
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发表时间：
1995
影响因子：
5.6
通讯作者：
A. Clarke
中科院分区：
文献类型：
--
作者：
N. Ranson;N. Dunster;S. Burston;A. Clarke
伴侣蛋白利用ATP水解产生的能量来提高蛋白质折叠的效率，其机制仍然是一个争论的问题。在这里，我们表明，线粒体苹果酸脱氢酶的自发和辅助折叠的动力学定量描述了一个简单的物理模型。蛋白质通过缓慢形成天然样单体从非天然链折叠，然后二聚化形成活性酶。错误折叠通过两个聚集阶段进行：第一阶段是缓慢可逆的，第二阶段是不可逆的。伴侣蛋白通过与ATP水解偶联的重复结合-释放循环加速第一次形成的不稳定聚集体的解离。通过这种催化作用，它们为生产性折叠途径提供单体，并阻断聚集的不可逆阶段，从而即使以亚化学计量的量存在时也保持最佳的折叠产率。水解活性伴侣蛋白是必需的，直到底物蛋白完成缓慢转变为其天然样单体状态。观察到的折叠速率和产率都通过这种机制增加，而不改变生产途径中的真实的速率。
Chaperonins use energy derived from ATP hydrolysis to enhance the efficiency of protein folding by a mechanism which remains a matter of debate. Here, we show that the kinetics of spontaneous and assisted folding of mitochondrial malate dehydrogenase are quantitatively described by a simple physical model. The protein folds from non-native chains by the slow formation of native-like monomers, which then dimerize to form the active enzyme. Misfolding proceeds by two phases of aggregation: the first is slowly reversible, the second is irreversible. Chaperonins accelerate the dissociation of the first-formed, unstable aggregates through a repeated binding-and-release cycle coupled to ATP hydrolysis. By this catalytic action, they supply the productive folding pathway with monomers, and block the irreversible phase of aggregation, thereby maintaining optimal folding yields even when present in sub-stoichiometric quantities. The hydrolytically active chaperonin is required until the substrate protein has completed the slow transition to its native-like, monomeric state. Both the observed rate of folding and the yield are increased by this mechanism without changing real rates in the productive pathway.