Net charge per residue modulates conformational ensembles of intrinsically disordered proteins
Net charge per residue modulates conformational ensembles of intrinsically disordered proteins
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DOI：
10.1073/pnas.0911107107
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发表时间：
2010-05-04
影响因子：
11.1
通讯作者：
Pappu, Rohit V.
中科院分区：
文献类型：
--
作者：
Mao, Albert H.;Crick, Scott L.;Pappu, Rohit V.
在生理条件下，内源性无序蛋白（IDPs）具有不同的构象。了解IDPs的氨基酸序列和构象集合之间的关系可以帮助阐明紊乱在生理功能中的作用。最近的研究表明，极性的IDPs喜欢在水中的崩溃合奏，尽管没有疏水基团的结果，以及持有的多肽骨架。通过研究高度带电的多肽，不同的原型的IDP，我们评估如何电荷含量调制多肽骨架的内在偏好塌陷的结构。我们采用分子模拟和荧光测量表征了一组鱼精蛋白在水环境中的构象集合。鱼精蛋白是富含精氨酸的IDP，参与精子发生过程中染色质的浓缩。ABSINTH隐式溶剂化模型的基础上的模拟预测存在一个球到线圈过渡，与净电荷作为判别序参数每个残基。模拟和实验之间的定量协议的过渡支持。局部构象偏好部分解释了所观察到的聚合物性质的趋势。我们的研究结果导致一个示意性的蛋白质相图的建议，应该能够预测的聚合属性IDP构象合奏使用容易计算的氨基酸序列的物理化学性质。虽然序列组合物允许预测的聚合物的性质，具有类似的聚合物属性的鱼精蛋白的残基间接触偏好表明，某些细节的构象合奏取决于序列。这为国内流离失所者的职能的特殊性提供了一个似乎合理的机制。
Intrinsically disordered proteins (IDPs) adopt heterogeneous ensembles of conformations under physiological conditions. Understanding the relationship between amino acid sequence and conformational ensembles of IDPs can help clarify the role of disorder in physiological function. Recent studies revealed that polar IDPs favor collapsed ensembles in water despite the absence of hydrophobic groups-a result that holds for polypeptide backbones as well. By studying highly charged polypeptides, a different archetype of IDPs, we assess how charge content modulates the intrinsic preference of polypeptide backbones for collapsed structures. We characterized conformational ensembles for a set of protamines in aqueous milieus using molecular simulations and fluorescence measurements. Protamines are arginine-rich IDPs involved in the condensation of chromatin during spermatogenesis. Simulations based on the ABSINTH implicit solvation model predict the existence of a globule-to-coil transition, with net charge per residue serving as the discriminating order parameter. The transition is supported by quantitative agreement between simulation and experiment. Local conformational preferences partially explain the observed trends of polymeric properties. Our results lead to the proposal of a schematic protein phase diagram that should enable prediction of polymeric attributes for IDP conformational ensembles using easily calculated physicochemical properties of amino acid sequences. Although sequence composition allows the prediction of polymeric properties, interresidue contact preferences of protamines with similar polymeric attributes suggest that certain details of conformational ensembles depend on the sequence. This provides a plausible mechanism for specificity in the functions of IDPs.