Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli" and Istituto di Biologia e Patologia Molecolari del CNR, Sapienza Università di Roma, 00185 Rome, Italy.
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli" and Istituto di Biologia e Patologia Molecolari del CNR, Sapienza Università di Roma, 00185 Rome, Italy.
J Mol Biol. 2021 Jul 23;433(15):167087. doi: 10.1016/j.jmb.2021.167087. Epub 2021 Jun 3.
Our current knowledge of protein folding is primarily based on experimental data obtained from isolated domains. In fact, because of their complexity, multidomain proteins have been elusive to the experimental characterization. Thus, the folding of a domain in isolation is generally assumed to resemble what should be observed for more complex structural architectures. Here we compared the folding mechanism of a protein domain in isolation and in the context of its supramodular multidomain structure. By carrying out an extensive mutational analysis we illustrate that while the early events of folding are malleable and influenced by the absence/presence of the neighboring structures, the late events appear to be more robust. These effects may be explained by analyzing the local frustration patterns of the domain, providing critical support for the funneled energy landscape theory of protein folding, and highlighting the role of protein frustration in sculpting the early events of the reaction.
我们目前对蛋白质折叠的了解主要基于从分离的结构域获得的实验数据。事实上，由于它们的复杂性，多结构域蛋白质一直难以通过实验进行特征描述。因此，通常假设孤立结构域的折叠类似于更复杂结构架构中应该观察到的折叠。在这里，我们比较了蛋白质结构域在孤立状态和超模块多结构域结构下的折叠机制。通过进行广泛的突变分析，我们说明尽管折叠的早期事件具有可变性并且受到相邻结构的缺失/存在的影响，但后期事件似乎更稳健。通过分析该结构域的局部受挫模式可以解释这些影响，这为蛋白质折叠的有槽能垒理论提供了重要支持，并突出了蛋白质受挫在塑造反应早期事件中的作用。
