Influence of local and residual structures on the scaling behavior and dimensions of unfolded proteins.
Influence of local and residual structures on the scaling behavior and dimensions of unfolded proteins.
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DOI：
10.1002/bip.20747
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发表时间：
2007-07
期刊：
影响因子：
2.9
通讯作者：
Zhisong Wang;K. Plaxco;D. Makarov
中科院分区：
文献类型：
--
作者：
Zhisong Wang;K. Plaxco;D. Makarov
虽然最近的化学变性蛋白质的光谱研究暗示在显着的非随机残留结构，广泛的小角度X射线散射研究的结果表明随机线圈的行为，呼吁这些看似矛盾的意见的连贯理解。在这里，我们报告的结果的Monte Carlo研究的两种类型的本地结构，α螺旋和聚脯氨酸II（PPII）螺旋，无规卷曲聚丙氨酸链的尺寸被视为高度变性蛋白质的模型的影响。我们发现，虽然弗洛里的幂律缩放，长期以来被认为是一个签名的随机线圈的行为，持有链含有高达90%的α或PPII螺旋，链尺寸的绝对大小是敏感的螺旋内容。随着残余α螺旋含量的增加，链收缩，直到它达到约70%螺旋的最小半径，之后链尺寸迅速扩大。与α螺旋含量约为20%，对应于拉马钱德兰的概率是在螺旋盆地，实验观察到的回转半径恢复。实验半径同样恢复在α螺旋含量约87%，提供了一个解释先前令人困惑的实验发现，高度螺旋甲醇诱导的未折叠状态的尺寸是实验上无法区分的螺旋穷人尿素未折叠状态。相反，回转半径随着PPII含量的增加而单调增加，并且总是比实验观察到的尺寸更大。这些结果表明，PPII不太可能是唯一的，占主导地位的未折叠蛋白质的首选构象。
Although recent spectroscopic studies of chemically denatured proteins hint at significant nonrandom residual structure, the results of extensive small angle X-ray scattering studies suggest random coil behavior, calling for a coherent understanding of these seemingly contradicting observations. Here, we report the results of a Monte Carlo study of the effects of two types of local structures, alpha helix and Polyproline II (PPII) helix, on the dimensions of random coil polyalanine chains viewed as a model of highly denatured proteins. We find that although Flory's power law scaling, long regarded as a signature of random coil behavior, holds for chains containing up to 90% alpha or PPII helix, the absolute magnitude of the chain dimensions is sensitive to helix content. As residual alpha helix content increases, the chain contracts until it reaches a minimum radius at approximately 70% helix, after which the chain dimensions expand rapidly. With an alpha helix content of approximately 20%, corresponding to the Ramachandran probability of being in the helical basin, experimentally observed radii of gyration are recovered. Experimental radii are similarly recovered at an alpha helix content of approximately 87%, providing an explanation for the previously puzzling experimental finding that the dimensions of the highly helical methanol-induced unfolded state are experimentally indistinguishable from those of the helix-poor urea-unfolded state. In contrast, the radius of gyration increases monotonically with increasing PPII content, and is always more expanded than the dimensions observed experimentally. These results suggest that PPII is unlikely the sole, dominant preferred conformation for unfolded proteins.