Kinetic trapping in protein folding
Kinetic trapping in protein folding
复制标题
蛋白质折叠中的动力学捕获
DOI：
10.1093/protein/gzz018
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Daggett, Valerie
中科院分区：
文献类型：
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作者：
Varela, Angela E;England, Kevin A;Cavagnero, Silvia;Daggett, Valerie
由Christian Anfinsen介绍的蛋白质折叠的基本原理，以及随后的许多机械研究，假设蛋白质折叠是一个受化学控制的过程。另一方面，这篇评论强调了这样一个事实，即热力学控制是远远不是蛋白质折叠的规范，只要一个人认为一个扩展的化学势景观，包括聚集体，除了原生的，未折叠的和中间状态。在这里，我们强调的关键作用，动力学捕获的蛋白质天然状态相对于未折叠，中间，最重要的是，聚集状态。我们建议，动力学捕获在生物学中起着重要的作用，通过保护大量蛋白质的生物活性状态免受有害的聚集。在以某种方式形成不期望的聚集体的情况下，专门的细胞内解聚机已经进化为将任何异常群体转化回天然状态，从而恢复完全生物活性和聚集保护的蛋白质组群。
The founding principles of protein folding introduced by Christian Anfinsen, together with the numerous mechanistic investigations that followed, assume that protein folding is a thermodynamically controlled process. On the other hand, this review underscores the fact that thermodynamic control is far from being the norm in protein folding, as long as one considers an extended chemical-potential landscape encompassing aggregates, in addition to native, unfolded and intermediate states. Here, we highlight the key role of kinetic trapping of the protein native state relative to unfolded, intermediate and, most importantly, aggregated states. We propose that kinetic trapping serves an important role in biology by protecting the bioactive states of a large number of proteins from deleterious aggregation. In the event that undesired aggregates were somehow formed, specialized intracellular disaggregation machines have evolved to convert any aberrant populations back to the native state, thus restoring a fully bioactive and aggregation-protected protein cohort.