Characterization of the unfolded state of repeat proteins.

Characterization of the unfolded state of repeat proteins.
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DOI:
10.2976/1.3021145
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发表时间:
2008-12
期刊:
影响因子:
--
通讯作者:
Levy, Yaakov
Levy, Yaakov
中科院分区:
其他
文献类型:
--
作者:
Mor, Amit;Haran, Gilad;Levy, Yaakov

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蛋白质的未折叠状态集合被描述为结构上无特征的状态。虽然这种方法得到了许多未折叠蛋白质遵循无规卷曲的标度律行为的事实的支持,但有证据表明各种蛋白质的未折叠状态通过天然或非天然相互作用而稳定。最近,广泛的非天然结构的存在下,重复蛋白质,这导致了标度律指数,这是显着小于随机聚合物的报道。得出的结论是,这种蛋白质的高紧凑性源于一个显着的部分相互作用的PPII螺旋段在未折叠状态。在这项研究中,我们的目的是提供可能的分子理解这种异常的紧凑性的展开状态,并调查其起源。使用层次结构的计算模型,我们问是否在一般的重复蛋白质的展开状态可能是本质上更紧凑的球状蛋白质的展开状态,或者这种现象是否主要取决于一个特定的序列,促进PPII构象的发生。我们的研究结果表明,PPII构象的形成确实是必不可少的,但重复蛋白的重复序列促进了这些PPII片段之间的相互作用和非天然相互作用在未折叠状态的形成。
The unfolded state ensemble of proteins has been described as a structurally featureless state. While this approach is supported by the fact that many unfolded proteins follow the scaling law behavior of a random coil, there is evidence that the unfolded states of various proteins are stabilized by native or non-native interactions. Recently, the existence of extensive non-native structure was reported for a repeat protein, which resulted in a scaling law exponent that is significantly smaller than that of a random polymer. It was concluded that the high compactness of this protein stems from a significant fraction of interacting PPII helical segments in the unfolded state. In this study, we aim at providing possible molecular understanding of this anomalous compactness of the unfolded state and to investigate its origin. Using a hierarchy of computational models, we ask whether in general the unfolded state of a repeat protein is likely to be intrinsically more compact than the unfolded state of globular proteins, or whether this phenomenon depends mostly on the occurrence of a specific sequence that promotes PPII conformations. Our results suggest that the formation of the PPII conformation is indeed essential, yet the recurring sequence of repeat proteins promotes the interactions between these PPII segments and the formation of non-native interactions in the unfolded state.
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