Understanding the structural ensembles of a highly extended disordered protein.
Understanding the structural ensembles of a highly extended disordered protein.
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DOI：
10.1039/c1mb05243h
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发表时间：
2012-01
影响因子：
--
通讯作者：
Ytreberg FM
中科院分区：
文献类型：
--
作者：
Daughdrill GW;Kashtanov S;Stancik A;Hill SE;Helms G;Muschol M;Receveur-Bréchot V;Ytreberg FM
对内在无序蛋白（IDPs）的平衡结构集合体进行全面描述对于理解其功能至关重要。p53反活化结构域（p53TAD）是一个与多个蛋白伴侣相互作用的IDP，包含许多磷酸化位点。采用多种技术研究了p53TAD在天然状态和化学未折叠状态下的平衡结构系综。这些实验结果表明，p53TAD的天然状态具有与经典随机线圈相似的尺寸，而化学展开状态则更加扩展。为了研究导致这种行为的分子特性，研究人员开发了一种新的算法，可以生成IDPs的多样性和无偏性结构集合。该算法被用来生成大量可信的p53TAD结构，这些结构被重新加权，以确定最适合小角度x射线散射数据的结构子集。天然状态集合中的高质量结构显示出定位于蛋白质结合位点和脯氨酸含量高的区域的特征。定位于蛋白质结合位点的特征在化学未折叠的集合中大部分被消除；而脯氨酸含量高的区域则相对不受影响。核磁共振实验数据支持这些结果，表明蛋白质结合位点的残基在尿素展开时比脯氨酸含量高的区域经历更大的环境变化。这种行为与尿素诱导的非极性和芳香侧链暴露在蛋白质结合位点一致，这些位点在天然状态集合中部分被溶剂排除在外。
Developing a comprehensive description of the equilibrium structural ensembles for intrinsically disordered proteins (IDPs) is essential to understanding their function. The p53 transactivation domain (p53TAD) is an IDP that interacts with multiple protein partners and contains numerous phosphorylation sites. Multiple techniques were used to investigate the equilibrium structural ensemble of p53TAD in its native and chemically unfolded states. The results from these experiments show that the native state of p53TAD has dimensions similar to a classical random coil while the chemically unfolded state is more extended. To investigate the molecular properties responsible for this behavior, a novel algorithm that generates diverse and unbiased structural ensembles of IDPs was developed. This algorithm was used to generate a large pool of plausible p53TAD structures that were reweighted to identify a subset of structures with the best fit to small angle X-ray scattering data. High weight structures in the native state ensemble show features that are localized to protein binding sites and regions with high proline content. The features localized to the protein binding sites are mostly eliminated in the chemically unfolded ensemble; while, the regions with high proline content remain relatively unaffected. Data from NMR experiments support these results, showing that residues from the protein binding sites experience larger environmental changes upon unfolding by urea than regions with high proline content. This behavior is consistent with the urea-induced exposure of nonpolar and aromatic side-chains in the protein binding sites that are partially excluded from solvent in the native state ensemble.
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影响因子：
6.8
作者：
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通讯作者：
Eliezer, David
DOI：
10.1073/pnas.0502269102
发表时间：
2005-07-05
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0506202102
发表时间：
2005-11-22
影响因子：
11.1
作者：
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通讯作者：
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DOI：
10.1073/pnas.0706251104
发表时间：
2007-09-25
影响因子：
11.1
作者：
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通讯作者：
Bolen, D. Wayne