Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Protein Eng Des Sel. 2019 Dec 13;32(2):103-108. doi: 10.1093/protein/gzz018.
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.
克里斯蒂安·安芬森（Christian Anfinsen）提出的蛋白质折叠的基本原则，以及随后进行的大量机制研究，都假设蛋白质折叠是一个热力学控制的过程。另一方面，本综述强调了一个事实，即在考虑包括聚集体在内的扩展化学势景观时，热力学控制远非蛋白质折叠的常态，除了天然、展开和中间状态。在这里，我们强调了蛋白质天然状态相对于展开状态、中间状态，尤其是聚集状态的动力学捕获的关键作用。我们提出，动力学捕获通过保护大量蛋白质的生物活性状态免受有害聚集，从而在生物学中发挥重要作用。如果以某种方式形成了不期望的聚集体，那么已经进化出了专门的细胞内解聚机器，将任何异常聚集体转换回天然状态，从而恢复具有完全生物活性和聚集保护的蛋白质群体。
