How Does a Simplified-Sequence Protein Fold?
How Does a Simplified-Sequence Protein Fold?
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DOI：
10.1016/j.bpj.2009.06.047
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发表时间：
2009-09-16
影响因子：
3.4
通讯作者：
Caflisch, Amedeo
中科院分区：
文献类型：
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作者：
Guarnera, Enrico;Pellarin, Riccardo;Caflisch, Amedeo
为了研究puericum原始蛋白，我们简化了56个残基的α/β折叠序列（蛋白G的免疫球蛋白结合结构域），在折叠结构中分别为α-螺旋、β-链和转角的序列区域用聚丙氨酸、聚苏氨酸和双甘氨酸片段取代。值得注意的是，在330 K的15 μ s分子动力学模拟中观察到多个折叠和去折叠事件。蛋白G的突变序列变体的最稳定状态（以类似于20%的比例填充）具有与野生型相同的α/β拓扑结构，但显示出熔融球的特征，即，侧链之间的松散接触和缺乏特定的疏水核心。未折叠状态是异质的，包括各种α/β拓扑结构，但也包括完全α-螺旋和完全β-折叠结构。在变性状态内的转变非常快，并且在10分钟内达到熔融球状态。
To investigate a putatively primordial protein we have simplified the sequence of a 56-residue alpha/beta fold (the immunoglobulin-binding domain of protein G) by replacing it with polyalanine, polythreonine, and diglycine segments at regions of the sequence that in the folded structure are alpha-helical, beta-strand, and turns, respectively. Remarkably, multiple folding and unfolding events are observed in a 15-mu s molecular dynamics simulation at 330 K. The most stable state (populated at similar to 20%) of the simplified-sequence variant of protein G has the same alpha/beta topology as the wild-type but shows the characteristics of a molten globule, i.e., loose contacts among side chains and lack of a specific hydrophobic core. The unfolded state is heterogeneous and includes a variety of alpha/beta topologies but also fully alpha-helical and fully beta-sheet structures. Transitions within the denatured state are very fast, and the molten-globule state is reached in