Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14609-14. doi: 10.1073/pnas.1001743107. Epub 2010 Jul 16.
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 Förster 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.
许多真核生物蛋白质在生理条件下是无规则的，只有与细胞靶标结合时才折叠成有规则的结构。这种无序蛋白质（IDP）通常含有大量带电荷的氨基酸。在这里，我们使用单分子Förster 共振能量转移来研究带电残基对未折叠和无序蛋白质尺寸的影响。我们发现，与在低变性剂浓度下观察到的许多蛋白质的紧凑无规构象相反，IDP 在低盐强度下会表现出明显的扩展，这与其净电荷有关。然而，电荷平衡的多肽在低盐强度下可以表现出额外的坍塌，这是由链中相反电荷之间的吸引力根据聚电解质理论预测的。电荷对未折叠蛋白质尺寸的显著影响对 IDP 的细胞功能具有重要意义。
