Charge interactions can dominate the dimensions of intrinsically disordered proteins
Charge interactions can dominate the dimensions of intrinsically disordered proteins
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DOI：
10.1073/pnas.1001743107
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发表时间：
2010-08-17
影响因子：
11.1
通讯作者：
Schuler, Benjamin
中科院分区：
文献类型：
--
作者：
Mueller-Spaeth, Sonja;Soranno, Andrea;Schuler, Benjamin
许多真核蛋白质在生理条件下是无序的，只有在与其细胞靶标结合时才会折叠成有序结构。这种本质上无序的蛋白质（IDP）通常含有大部分带电荷的氨基酸。在这里，我们使用单分子福斯特共振能量转移来研究带电残基对未折叠和本质无序蛋白质尺寸的影响。我们发现，与许多蛋白质在低变性剂浓度下观察到的紧凑的未折叠构象相反，IDP 在低离子强度下可以表现出显着的扩张，这与其净电荷相关。然而，电荷平衡的多肽在低离子强度下可能会表现出额外的塌陷，正如聚两性电解质理论根据链中相反电荷之间的吸引力所预测的那样。电荷对未折叠蛋白质尺寸的显着影响对于 IDP 的细胞功能具有重要意义。
Many eukaryotic proteins are disordered under physiological conditions, and fold into ordered structures only on binding to their cellular targets. Such intrinsically disordered proteins (IDPs) often contain a large fraction of charged amino acids. Here, we use single-molecule Forster resonance energy transfer to investigate the influence of charged residues on the dimensions of unfolded and intrinsically disordered proteins. We find that, in contrast to the compact unfolded conformations that have been observed for many proteins at low denaturant concentration, IDPs can exhibit a prominent expansion at low ionic strength that correlates with their net charge. Charge-balanced polypeptides, however, can exhibit an additional collapse at low ionic strength, as predicted by polyampholyte theory from the attraction between opposite charges in the chain. The pronounced effect of charges on the dimensions of unfolded proteins has important implications for the cellular functions of IDPs.